diff --git a/docs/src/whatsnew/latest.rst b/docs/src/whatsnew/latest.rst
index 825508dca3..d4d5cb499a 100644
--- a/docs/src/whatsnew/latest.rst
+++ b/docs/src/whatsnew/latest.rst
@@ -36,7 +36,10 @@ This document explains the changes made to Iris for this release
 🐛 Bugs Fixed
 =============
 
-#. N/A
+#. :user:`gaoflow` made :class:`iris.Constraint` raise a ``TypeError`` when used
+   in a boolean context (e.g. with the ``and``/``or``/``not`` keywords) instead
+   of silently discarding one of the constraints. Use the ``&`` operator to
+   combine constraints. (:issue:`4337`)
 
 
 💣 Incompatible Changes
diff --git a/lib/iris/_constraints.py b/lib/iris/_constraints.py
index c0ba2f120f..d3d682e89e 100644
--- a/lib/iris/_constraints.py
+++ b/lib/iris/_constraints.py
@@ -218,6 +218,18 @@ def __and__(self, other):
     def __rand__(self, other):
         return ConstraintCombination(other, self, operator.__and__)
 
+    def __bool__(self):
+        # Constraints have no truth value: combining them with the Python
+        # keywords ``and``/``or``/``not`` (which call bool()) silently returns
+        # one of the operands instead of a combined Constraint, losing the
+        # other. Raise an explanatory error so this is not a silent failure;
+        # use the ``&`` operator to combine constraints. See #4337.
+        raise TypeError(
+            "The truth value of a Constraint is ambiguous. Constraints cannot "
+            "be combined with the 'and', 'or' and 'not' keywords; use the '&' "
+            "operator instead, e.g. 'constraint1 & constraint2'."
+        )
+
 
 class ConstraintCombination(Constraint):
     """Represents the binary combination of two Constraint instances."""
diff --git a/lib/iris/tests/unit/constraints/test_Constraint__bool__.py b/lib/iris/tests/unit/constraints/test_Constraint__bool__.py
new file mode 100644
index 0000000000..5b48de32eb
--- /dev/null
+++ b/lib/iris/tests/unit/constraints/test_Constraint__bool__.py
@@ -0,0 +1,68 @@
+# Copyright Iris contributors
+#
+# This file is part of Iris and is released under the BSD license.
+# See LICENSE in the root of the repository for full licensing details.
+"""Unit tests for :meth:`iris._constraints.Constraint.__bool__`."""
+
+import operator
+
+import pytest
+
+from iris._constraints import (
+    AttributeConstraint,
+    Constraint,
+    ConstraintCombination,
+    NameConstraint,
+)
+
+
+class Test_Constraint__bool__:
+    # Using a Constraint in a boolean context (e.g. with the ``and``/``or``/
+    # ``not`` keywords) used to silently return one of the operands, quietly
+    # discarding the other. It should instead raise an informative TypeError
+    # so the user is directed towards the ``&`` operator (see #4337).
+
+    _match = "truth value of a Constraint is ambiguous"
+
+    def test_bool(self):
+        with pytest.raises(TypeError, match=self._match):
+            bool(Constraint("air_temperature"))
+
+    def test_keyword_or(self):
+        c1 = Constraint("air_temperature")
+        c2 = Constraint("time")
+        with pytest.raises(TypeError, match=self._match):
+            c1 or c2
+
+    def test_keyword_and(self):
+        c1 = Constraint("air_temperature")
+        c2 = Constraint("time")
+        with pytest.raises(TypeError, match=self._match):
+            c1 and c2
+
+    def test_keyword_not(self):
+        with pytest.raises(TypeError, match=self._match):
+            not Constraint("air_temperature")
+
+    def test_constraint_combination(self):
+        combination = ConstraintCombination(
+            Constraint("air_temperature"),
+            Constraint("time"),
+            operator.__and__,
+        )
+        with pytest.raises(TypeError, match=self._match):
+            bool(combination)
+
+    def test_attribute_constraint(self):
+        with pytest.raises(TypeError, match=self._match):
+            bool(AttributeConstraint(STASH="m01s00i024"))
+
+    def test_name_constraint(self):
+        with pytest.raises(TypeError, match=self._match):
+            bool(NameConstraint(standard_name="air_temperature"))
+
+    def test_and_operator_still_works(self):
+        # The supported way of combining constraints must be unaffected.
+        c1 = Constraint("air_temperature")
+        c2 = Constraint("time")
+        assert isinstance(c1 & c2, ConstraintCombination)