Peroxisome proliferator-activated receptor alpha ($PPAR\alpha$) is expressed throughout the mammalian gut: in epithelial cells, in the villi of enterocytes and in Paneth cells of intestinal crypts, as well as in some immune cells (e.g., lamina propria macrophages, dendritic cells) of the mucosa. This review examines the reciprocal interaction between $PPAR\alpha$ activation and intestinal microbiota. We refer to the published data confirming that microbiota products can influence $PPAR\alpha$ signaling and, on the other hand, $PPAR\alpha$ activation is able to affect microbiota profile, viability, and diversity. $PPAR\alpha$ impact on the broad spectrum of events connected to metabolism, signaling (e.g., NO production), immunological tolerance to dietary antigens, immunity and permeability of the gut are also discussed. We believe that the phenomena described here play a prominent role in gut homeostasis. Therefore, in conclusion we propose future directions for research, including the application of synthetic activators and natural endogenous ligands of $PPAR\alpha$ (i.e., endocannabinoids) as therapeutics for intestinal pathologies and systemic diseases assumed to be related to gut dysbiosis.