Inflammatory bowel disease (IBD) is a condition that is subject to genetic and environmental factors, characterized by multifaceted proinflammatory responses, which consequently can affect both hematological and non-hematological structures in the intestines. Gut microbiota dysbiosis is an environmental trigger posited to dysregulate the local immune system, initiating a complex interplay with a genetic predisposition to maintain the condition. Medicinal cannabis investigations on their anti-inflammatory characteristics have not been consistent with reports from laboratory studies with murine models. Although oral administration of medicinal cannabis, single molecules, or as mixed extracts from the flowering plant has been deemed safe, human clinical studies have not provided objective anti-inflammatory efficacy for conditions such as IBD. Anti-inflammatory efficacy was not observed for either ulcerative colitis (UC) or Crohn's disease (CD) with either Δ9-Tetrahydrocannabinol + Cannabidiol (Δ9-THC + CBD) or CBD alone, while improving the quality of life (QoL) of patients diagnosed with IBD. Mechanistically, what the current research shows is that the endocannabinoid system (ECS) tone in the gut is subject to intestinal microbiota homeostasis. Intestinal dysbiosis, as described for IBD, is posited to disturb the tone of the ECS, thereby disrupting the effects that medicinal cannabis may have in the treatment of gut inflammation. Conditions of IBD are linked with gut and vermiform appendix microbiota dysbiosis, characteristics in the colon that may destabilize the tone of the ECS and lead to medicinal cannabis failures to achieve clinically objective anti-inflammatory effects. The aim of this review is to investigate the link between the intestinal microbiota, the ECS and IBD. The quick, natural fix that medicinal cannabis appears to provide to manage the underlying IBD disease may not be suitable for all patients diagnosed with UC or CD.