Capsicum spp. fruits (CFs) are a basic ingredient in the diet and have been used as active ingredients in the pharmaceutical, cosmetic, and food products, due to their antioxidant, anti-inflammatory, antiseptic, and antimicrobial properties. The antimicrobial activity is the most studied property due to its effectiveness against pathogenic species, however, few studies have focused on the mechanisms of action involved. Therefore, this review discusses the effects generated by the CFs compounds on the viability and metabolism of microorganisms, highlighting the mechanisms by which these compounds exert their antimicrobial effects. The information provided shows that CFs are mainly source of capsaicinoids and phenolic compounds responsible for the inhibition of bacteria, yeasts, and fungi, through an increase in the permeabilization of the membrane and cell wall. Also, these compounds show an antiviral effect associated with the inactivation of virus binding proteins, preventing their replication and infection. Despite this, there is still a lack of information about the mechanisms that regulate the interactions between CFs compounds and food-important-microorganisms. Therefore, future research should focus on new antimicrobial compounds from CFs for their subsequent use against novel infectious agents, mainly virus of importance in health such as SARS-CoV-2.