In today's context of an aging population and the gradual decline of human physiological functions, we are increasingly confronted with health issues such as fractures and arthritis. The demand for implants has risen correspondingly, while traditional alloys have become insufficient to meet the developmental needs of this era. The emergence of multi-principal element alloys (or high-entropy alloys) in 2004 has attracted significant attention, leading to extensive research due to their remarkable four core effects. Currently, multi-principal element alloys are gradually demonstrating their potential in the biomedical field. Therefore, a review of multi-principal element alloys in biomedical applications is of high interest. This paper explores the key considerations in the design of biological multi-principal element alloys, focusing on the latest research advancements in areas such as orthopedic implants, dentistry, and cardiovascular stents. We analyze their advantages in mechanical properties and biocompatibility while introducing their preparation methods. Furthermore, the article discusses the challenges faced by biological multi-principal element alloys in current research and anticipates future development directions for these materials. The primary objective of this review is to show the potential applications of multi-principal element alloys in implants, ensuring that the discussion remains engaging and novel. We aim to provide a reference to facilitate development of multi-principal element alloys for practical applications in the biomedical field.