Gradient structures found in biological materials have served as a source of inspiration for scientists seeking to enhance the performance of metals and alloys over the past decades. These gradient-structured metals and alloys have manifested themselves with unprecedented mechanical properties as compared to their homogeneous counterparts, including superior strength–ductility synergy, high fracture toughness, and enhanced resistance to fatigue, wear, and corrosion. This review is devoted to providing a critical evaluation of the up-to-date research on gradient-structured metals and alloys, including the emerging fabrication techniques and fundamental mechanisms contributing to their strengthening, strain hardening, and ductility. We also provide a comprehensive summary of the mechanical properties of metals and alloys with structural gradients from experimental, theoretical, and modeling perspectives, as well as design strategies to tailor the properties. Finally, the potential applications and prospects of designing gradient-structured metals and alloys are discussed.