In recent years, the green synthesis of different metal nanoparticles has become a substantial technique for the synthesis of different essential nanoparticles and their potential applications in technological, industrial along with biomedical fields. Among the several essential nanoparticles, copper nanoparticles (CuNPs) have been attracted enormous attention for their wide range of applications like production of gas sensors, solar cells, high temperature superconductors as well as drug delivery materials and catalysis owing to its distinctive optical, electrical, dielectric, imaging and catalytic, etc. properties. Herein, in this review, our aim is to find out the recent progress of synthesis as well as different optical and structural characterizations of green synthesized CuNPs along with their broad-spectrum biomedical applications, mainly antibacterial, antifungal, antiviral and anticancer as well as the future perspective of research trends in the green synthesis of CuNPs. CuNPs have been synthesized by different researchers using three methods, namely, physical, chemical, and biological. In this review, the eco-friendly, efficient and low cost different established biological/green synthesis methods of CuNPs using different plant extracts like leaves, flowers, fruits, seeds, latex, etc., as capping and reducing agents have been briefly discussed along with reaction conditions together with their optical as well as structural analysis. Effects of different parameters on the green synthesis of CuNPs like presence of phytochemicals and confirmation of phytochemicals, temperperature, pH, etc. are elucidated. Studies of the antibacterial activity of biomolecules capped CuNPs by different researchers against both Gram positive and Gram-negative bacterial strains along with minimum inhibitory concentration (MIC) values have been summarized. Furthermore, antifungal and antiviral effects of green synthesized CuNPs studied by different researchers are mentioned with minimum inhibitory concentration (MIC) values. The anticancer activity of green synthesized CuNPs against different cancer cells that studied by different researchers are summarized with corellation sizes of CuNPs on anticancer activity. The review also focuses on in vivo applications of green synthesized CuNPs along with clinical trails. Furthermore, an emphasis is given on effectiveness of CuNPs to combating COVID-19.