KPV, a tripeptide (Lys-Pro-Val) derived from the C-terminal sequence of α-melanocyte-stimulating hormone (α-MSH), has been investigated in cellular and biochemical models for its anti-inflammatory and antimicrobial properties, primarily through inhibition of NF-κB activation and mitogen-activated protein kinase (MAPK) signaling pathways, leading to reduced secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in stimulated epithelial and immune cells. In vitro studies on bronchial epithelial cells and keratinocytes demonstrate that nanomolar concentrations of KPV suppress inflammation cues triggered by oxidative stress or fine particulate matter, modulating redox-sensitive pathways and attenuating apoptosis via antioxidant mechanisms, while its uptake is facilitated by the PepT1 transporter in intestinal models, enhancing its localized effects on inflammatory signaling. Additionally, research highlights KPV’s antimicrobial activity against pathogens like Candida species, particularly in dimeric forms, and its role in stabilizing tight junctions to maintain barrier integrity in gut epithelial analogs, positioning it as a tool for exploring immunomodulatory dynamics in controlled experimental environments without the broader hormonal impacts of full-length α-MSH.