With legalisation of cannabis for both medicinal and recreational use expanding to more world nations, grasping its effects on the human body is vital. The microbiome is critical to human health and disease, and accumulating data suggests that it is influenced by a variety of external variables, including marijuana/cannabis and cannabinoids. We therefore conducted a comprehensive assessment of the literature to analyse cannabis and cannabinoid effects on the human microbiota. We searched PubMed, Embase and Cochrane Library CENTRAL databases for studies involving the use of marijuana, medical cannabis, cannabinoids and cannabinoid-like lipid mediators on microbiota, across all clinical conditions. Nine studies were identified: 2 clinical trials and 7 observational studies examining cannabis and cannabinoid impact on oral, gastrointestinal, faecal and vaginal microbial abundance and diversity. Outcomes illustrated positive and negative impacts of cannabis use/cannabinoid actions on microbiota in adults with cognitive deficiency, depression, HIV infection, inflammation/pain, oral disease or obesity. Changes in alpha diversity were identified with cannabis/cannabinoid use, although this varied depending on the clinical context. A positive association exists between serum endocannabinoids and gut microbiota, via elevation in SCFAs and anti-inflammatory actions, beneficial for musculoskeletal pain relief and to counter obesity. Marijuana use in HIV patients showed protective effects by decreasing abundance of pro-inflammatory Prevotella, though excessive consumption leads to reduced microbiome richness and diversity, and increased systemic inflammation. Overall, this review underscores the need for further exploration in understanding the complex effects of cannabis, cannabinoids and cannabinoid-like mediators on composition and metabolic activity of the human microbiota.