A significant portion of the human diet is comprised of fruits, which are consumed globally either raw or after being processed. A huge amount of waste and by-products such as skins, seeds, cores, rags, rinds, pomace, etc. are being generated in our homes and agro-processing industries every day. According to previous statistics, nearly half of the fruits are lost or discarded during the entire processing chain. The concern arises when those wastes and by-products damage the environment and simultaneously cause economic losses. There is a lot of potential in these by-products for reuse in a variety of applications, including the isolation of valuable bioactive ingredients and their application in developing healthy and functional foods. The development of novel techniques for the transformation of these materials into marketable commodities may offer a workable solution to this waste issue while also promoting sustainable economic growth from the bio-economic viewpoint. This approach can manage waste as well as add value to enterprises. The goal of this study is twofold based on this scenario. The first is to present a brief overview of the most significant bioactive substances found in those by-products. The second is to review the current status of their valorization including the trends and techniques, safety assessments, sensory attributes, and challenges. Moreover, specific attention is drawn to the future perspective, and some solutions are discussed in this report.