The search for a new antibiotic or antifungal that could function efficiently without side effects or inadequacies was always a dilemma. For centuries, mushrooms have been praised for their medicinal powers. Recent studies show that many mushroom species possess antimicrobial compounds that inhibit or kill bacteria, fungi, and other microbes. These studies attributed the antimicrobial potency of mushrooms to the presence of active compounds called phytochemicals. Mushrooms have been found to contain an abundance of phytochemicals such as phenolics, terpenoids, flavonoids, alkaloids, steroids, saponins, and polysaccharides. These compounds can inhibit cell wall synthesis and disrupt membrane permeability or redox balance. This review highlights the current knowledge about the phytochemical content of mushrooms, their antimicrobial properties, and some extraction strategies. The antimicrobial effects of various microorganisms, such as foodborne pathogens, drug‐resistant bacteria, and fungi, are discussed. Critical limitations in using mushrooms as antimicrobial sources include safety risks from toxins, variability in compound potency between species, extraction and purification challenges, inconsistent yields, scalability issues, and regulatory hurdles for commercial applications. Overall, this article shows that mushrooms are prosperous of various antimicrobial compounds that can benefit human health.