Aim: Inhibition of enzymes catalyzing the production of metabolites that predispose to metabolic diseases is an important index of the potential health benefits of natural products. In this study, the ability of guava (Psidium guajava Linn.) stem bark phenolics-rich extract to inhibit enzymes associated with nephrolithiasis (xanthine oxidase and urease) and obesity [pancreatic lipase and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase] was evaluated in vitro. Methods: The phenolics profile of the extract was determined using HPLC-DAD; while the enzymes inhibitory and anti-radical properties of the extract were tested using spectrophotometric methods. Results: HPLC-DAD fingerprinting revealed that ellagic acid and quercetin were the most abundant phenolic acid and flavonoids, respectively, in the extract. The extract inhibited xanthine oxidase, urease, pancreatic lipase and HMG-CoA reductase, with IC50 values below 40 μg/mL. The extract also exhibited potent anti-radical activity by scavenging ABTS*+, DPPH* and chelating F2+. Conclusions: Hence, guava stem bark may be a source of nutraceuticals for suppressing the production of uric acid, ammonium hydroxide, fatty acids and cholesterol, and mitigating oxidative stress. These bioactivities, which can be attributed to the phenolic compounds, suggest anti-nephrolithiatic and anti-obesity potentials of guava stem bark phenolics-rich extract.