The plant pathogens result in crop damage of 30–40%, and dependence on chemical pesticides to combat these pathogens has led to resistance problem in phytopathogens. The various side effects of use of agrochemicals have sparked the interest of scientists toward sustainable agriculture that favors biological pesticides over chemical pesticides. Among microbes, having potential to use in sustainable agriculture as safe alternatives to chemical pesticides or fertilizers, members of genus Streptomyces in phylum Actinobacteria hold significant position. Streptomyces species produce a wide range of antimicrobial compounds, including antibiotics, volatile organic compounds, cyclic peptides and alkaloid derivatives, and lytic enzymes, which effectively mitigate bacterial and fungal pathogens in agriculture. Using diverse modes of operation (synthesis of different classes of antibiotics, lytic enzymes, volatiles, etc.), Streptomycetes has gained the status of good Microbial Biological Control Agents (MBCA). Metabolomics profiling of several Streptomyces species has exemplified the presence of bioactive metabolites with both growth-promoting and antifungal properties, such as tetrangulol, indole-3-acetamide, nicotinic acid, and N-succinyl-L-glutamate. Streptomyces metabolites promote overall plant growth, nutrient uptake, and phytohormone regulation. Although many Streptomyces species have been explored and employed in the manufacturing of commercial products, their role in the biocontrol of plant pathogens and mechanisms of functional metabolite synthesis remain poorly understood. This chapter further emphasizes the significance of bioactive compounds produced by Streptomyces in combating plant pathogens that threaten crop productivity, while simultaneously enhancing soil health.