Copper (Cu) is an inexpensive transition metal on Earth, exhibiting high catalytic activity due to its rich d-electron configuration and variable oxidation states. Cu-based biological alloys and nanocomposites have emerged as a prominent research area. Under specific synthesis conditions, alloys or nanocomposites formed by Cu with other metals demonstrate excellent enzyme-like and sensing activities. These advanced materials offer significant advantages over artificial enzymes in enzymatic applications, including high stability, simple synthesis, flexible catalytic performance, and ease of preservation. In addition, various types of sensors have been designed based on the unique electrochemical properties exhibited by these alloys and nanocomposites as well as their specific reactions with the target substances. These sensors possess advantages such as stability, high efficiency, a broad detection range, low detection limits, and high sensitivity. In this review, we summarize the current research status of Cu-based biological alloys and nanocomposites in enzyme-like applications and sensing applications. Based on this, we introduce the diverse enzyme-like activities exhibited by Cu-based nanozymes prepared under different synthesis conditions and their applications in areas such as biosensing, cancer treatment, and antibacterial therapy. Furthermore, we provide an overview of the applications of Cu-based alloys and nanocomposites in the field of sensing based on their enzyme-like activity or chemical activities. These sensors have been widely employed in biomedical detection, environmental hazardous substance monitoring, and food safety testing. Challenges and prospects faced by Cu-based alloys and nanocomposites are also highlighted for future works.