The world is currently facing an increase in multi-drug resistance which is a serious threat to global health. Owing to this, and the scarcity of novel synthetic drugs on the market, the researchers are encouraged to find new means to combat the multi-drug resistance pathogens, directed towards utilizing natural bioactive products that have potent effectiveness and are harmless to humans. Microorganisms synthesize these compounds either alone or alongside plants. Endophytic bacteria colonize the inside tissues of the plant, with no disease symptoms appearing on plant tissues. The extensive colonization of endophytic bacteria inside plant tissues forms a barrier that prevents harmful pathogens from taking hold. This occurs by creating secondary metabolites that inhibit the growth of pathogenic organisms. In this regard, they have an essential role in plant defensive systems. Thus, the goal of this article is to provide a broad overview of the current screening and production strategies for novel bacterial endophytes-derived compounds that have antimicrobial, antibacterial, antifungal, antiviral, antioxidant, and anticancer activities, as well as to present their potential applications in the pharmaceutical, medicinal, agricultural, and food industries.