PURPOSE OF REVIEW: This review explores how cannabis impacts the gut microbiome, immune system, and ART outcomes in people with HIV (PWH). Given the increasing prevalence of cannabis use among PWH, we investigated its potential to reduce chronic inflammation and enhance gut health, both of which can influence HIV pathogenesis. RECENT FINDINGS: Cannabis has immunomodulatory and anti-inflammatory effects, including reducing systemic inflammatory biomarkers (such as MCP-1 and IP-10) and improving gut barrier integrity through increased short-chain fatty acid (SCFA) production. Studies have shown that cannabis use is associated with increased gut mucosal immunity, decreased immune activation, and a unique microbiome composition. Preliminary evidence indicates that cannabis may influence HIV reservoirs, although the results remain inconclusive. Cannabis shows promise in managing inflammation, gut dysbiosis, and immune dysfunction in PWH. However, its effects on HIV reservoirs, adherence to antiretroviral therapy, and long-term outcomes need further investigation through rigorous clinical trials using standardized formulations.