This chapter outlines recent advancements in the design of artificial metalloenzymes and their applications as catalysts. The integration of enzymes with metals to create these novel systems has emerged as a highly promising area of research. A key challenge lies in developing artificial metalloenzymes that mimic enzyme-like activities, such as reduction, oxidation, hydrolysis, and C–C bond formation. The chapter explores innovative approaches for creating these systems, including directed evolution, organometallic-protein conjugation, and nanobiohybrids.