Oil palm phenolics (OPP), recovered from aqueous side streams generated during oil-palm fruit processing, provide an unusual link between circular bioeconomy, phytochemical biotechnology, microbiome science, and metabolic medicine. This qualitative literature review critically evaluates whether OPP could progress from an underutilized palm-processing fraction to a microbiome-mediated nutritional intervention for obesity, prediabetes, and type 2 diabetes mellitus (T2DM). The review integrates evidence concerning OPP composition and human safety, gastrointestinal transformation of dietary polyphenols, microbial ecology, short-chain fatty acids, bile-acid metabolism, phenolic microbial metabolites, intestinal-barrier integrity, lipopolysaccharide-mediated metabolic endotoxemia, chronic inflammation, and insulin signaling. Direct clinical evidence remains limited: human research principally establishes short-term OPP safety rather than therapeutic efficacy. Nevertheless, experimental evidence demonstrates that palmderived phenolic residues can alter obese-human fecal microbial communities and generate microbial phenolic metabolites. Broader human polyphenol research further supports modulation of microbiota and metabolic-endotoxemia-related endpoints, although effects on body weight, inflammation, and glycemic outcomes remain heterogeneous. This review proposes an integrated OPP– microbiome–intestinal barrier–metabolic inflammation–insulin resistance axis and identifies a translational evidence ladder from chemical standardization through microbiome-stratified clinical trials. OPP should currently be viewed as a promising microbiomeactive candidate rather than an established antidiabetic nutraceutical.