diff --git a/src/qc_compiler/autotuning.py b/src/qc_compiler/autotuning.py
index b909ade..fd79ac9 100644
--- a/src/qc_compiler/autotuning.py
+++ b/src/qc_compiler/autotuning.py
@@ -61,6 +61,16 @@ class TranspileConfig:
     gate_fusion: bool = True
     scheduling_method: str = "coherence_aware"
 
+    def __post_init__(self):
+        if not isinstance(self.optimization_level, int) or not 0 <= self.optimization_level <= 3:
+            raise ValueError(
+                f"optimization_level must be 0-3, got {self.optimization_level}."
+            )
+        if not isinstance(self.seed, int) or self.seed < 0:
+            raise ValueError(
+                f"seed must be a non-negative integer, got {self.seed}."
+            )
+
     def config_key(self) -> str:
         """Generate a unique string key for this configuration."""
         return (
diff --git a/src/qc_compiler/transpiler.py b/src/qc_compiler/transpiler.py
index 8d30485..a52a9c0 100644
--- a/src/qc_compiler/transpiler.py
+++ b/src/qc_compiler/transpiler.py
@@ -59,6 +59,21 @@ class OptimizerConfig:
     batch: bool = True
     autotune: bool = False
 
+    def __post_init__(self):
+        valid_mitigation = {"adaptive", "zne", "pec", "cdr", "none"}
+        valid_scheduling = {"asap", "alap", "coherence_aware", "none"}
+
+        if self.mitigation not in valid_mitigation:
+            raise ValueError(
+                f"Invalid mitigation '{self.mitigation}'. "
+                f"Choose from {valid_mitigation}."
+            )
+        if self.scheduling not in valid_scheduling:
+            raise ValueError(
+                f"Invalid scheduling '{self.scheduling}'. "
+                f"Choose from {valid_scheduling}."
+            )
+
 
 @dataclass
 class QCompilerResult:
@@ -171,6 +186,11 @@ def optimize(
         if config is None:
             config = OptimizerConfig()
 
+        if circuit is None:
+            raise ValueError("circuit must not be None")
+        if circuit.num_qubits == 0:
+            raise ValueError("circuit must have at least one qubit")
+
         result = QCompilerResult(
             original_circuit=circuit.copy(),
             config=config,
diff --git a/tests/test_autotuning.py b/tests/test_autotuning.py
index 9d30277..bc1918c 100644
--- a/tests/test_autotuning.py
+++ b/tests/test_autotuning.py
@@ -320,4 +320,25 @@ def test_search_space_covers_all_optimization_levels(self):
         tuner = AutoTuner(cost_model=CostModel())
         configs = tuner._generate_configurations()
         opt_levels = {c.optimization_level for c in configs}
-        assert opt_levels == {1, 2, 3}
\ No newline at end of file
+        assert opt_levels == {1, 2, 3}
+
+
+class TestTranspileConfigValidation:
+    """Regression tests for TranspileConfig validation (issue #59)."""
+
+    def test_invalid_optimization_level_raises(self):
+        with pytest.raises(ValueError, match="optimization_level"):
+            TranspileConfig(optimization_level=5)
+
+    def test_negative_seed_raises(self):
+        with pytest.raises(ValueError, match="seed"):
+            TranspileConfig(seed=-1)
+
+    def test_valid_config_does_not_raise(self):
+        config = TranspileConfig(
+            routing_method="stochastic",
+            layout_method="dense",
+            optimization_level=2,
+            seed=42,
+        )
+        assert config.optimization_level == 2
\ No newline at end of file
diff --git a/tests/test_transpiler.py b/tests/test_transpiler.py
index b631d65..b9c5e90 100644
--- a/tests/test_transpiler.py
+++ b/tests/test_transpiler.py
@@ -392,4 +392,26 @@ def test_cutting_with_scheduling_applies_to_subcircuits(self):
         assert result.cutting_result is not None
         if result.cutting_result.should_cut and result.subcircuits is not None:
             assert len(result.subcircuits) > 1
-            assert result.fidelity_after > 0
\ No newline at end of file
+            assert result.fidelity_after > 0
+
+
+class TestInputValidation:
+    """Regression tests for input validation (issue #59)."""
+
+    def test_none_circuit_raises(self):
+        compiler = QCompiler()
+        with pytest.raises(ValueError, match="circuit must not be None"):
+            compiler.optimize(None)
+
+    def test_empty_circuit_raises(self):
+        compiler = QCompiler()
+        with pytest.raises(ValueError, match="at least one qubit"):
+            compiler.optimize(QuantumCircuit(0))
+
+    def test_invalid_mitigation_raises(self):
+        with pytest.raises(ValueError, match="Invalid mitigation"):
+            OptimizerConfig(mitigation="invalid")
+
+    def test_invalid_scheduling_raises(self):
+        with pytest.raises(ValueError, match="Invalid scheduling"):
+            OptimizerConfig(scheduling="invalid")
\ No newline at end of file