► Crude caffeine is an intermediate by-product produced during the decaffeination process. ► We discovered that crude caffeine possessed unexpected bioactive properties. ► Crude caffeine had antioxidant activities, inhibited COX-2, and increased glucose uptakes. ► Pure caffeine, accounting for ∼90% of the crude caffeine mass, had negligible such bioactivities. ► Crude caffeine may serve as a novel functional ingredient in the food industry. Thousands of tons of crude caffeine are produced annually in the decaffeination of coffee. Crude caffeine is further purified to obtain pure caffeine, and the non-caffeine residue is typically discarded as waste. In the present study, we discovered that crude caffeine possessed unexpected bioactive properties. Crude caffeine had potent hydrophilic antioxidant activity (145μmol Trolox equivalent (TE)/g) and lipophilic antioxidant activity (66μmol TE/g). It also inhibited cyclooxygenase-2 with a higher potency (IC50, 20μg/ml) than 2-acetoxybenzoic acid (aspirin, IC50, 190μg/ml). Crude caffeine increased glucose uptake 1.45-fold in cultured human skeletal muscle cells and 2.20-fold in adipocytes. In contrast, pure caffeine, which accounts for approximately 90% of the crude caffeine mass, was found to possess negligible antioxidant activity and did not inhibit cyclooxygenase-2, nor stimulate glucose uptake. We believe crude caffeine has potential health benefits and may serve as a novel functional ingredient in the food industry.