With the increasing concern over the environmental impact of conventional chemical methods, environmentally friendly processes, commonly known as green chemistry, for the synthesis of nanoparticles have gained growing interest in the field of nanobiotechnology. This review focuses on synthesis of metallic nanoparticles (NPs) based on green chemistry and their applications as new drug delivery system in anticancer and antimicrobial treatment. The review encompasses a survey of the production and characterization of green synthetic NPs, along with an examination of their physico-chemical properties and biological activities. Notably, this review goes beyond previous reports by providing an extensive analysis of recent studies that utilize in silico design for the green synthesis of nanoparticles and computational modeling to gain deeper insights into the interactions between these NPs and their targets. The simulation helps not only with comprehending the biological mechanism of NPs, but also with predicting any potential bioactivities. By offering a broad perspective and novel ideas, this review attempts to shed light on the future of green chemistry in the development of smart medicine and modern generation of cancer therapy and other disease treatments.