Total phenolic, flavonoid, and tannin contents of 21 Ethiopian khat (Catha edulis Forsk) leaves and their related antioxidant activities were determined in the extracts of the young leaves, matured leaves, and tips of tender stem near the young shoots. A simplified, rapid, and robust method was also optimized for the analysis of total tannins using ovalbumin as a precipitating agent and Folin Denis reagent as the quantification technique. Among the solvents tested, aqueous mixtures of 70 and 80% acetone and 80% methanol provided higher phenolic compounds extraction efficiency than the corresponding pure solvents and other binary mixtures. Results of the analysis revealed that total phenols ranged from 129 to 274 mg tannic acid equivalent/g of dried young leaves and 89.3 to 175 mg tannic acid equivalent/g of dried tender stem tips. Total tannin content ranged between 70.2−153 mg tannic acid equivalent/g and 49.4−103 mg tannic acid equivalent/g of the dried young leaves and tips of tender stems, respectively. Similarly, total flavonoids concentration as catechin equivalent varied between 26 to 75 and 26 to 56 mg catechin equivalent/g of dried young leaves and tips of tender stems, respectively. Khat cultivars were found to pose a substantial antioxidative activity (as ascorbic acid equivalent) ranging between 173−290 and 118−211 mg ascorbic acid equivalent/g of dried young leaves and tips of tender stems near the young shoot, respectively. Matured leaves of khat accumulated a significantly lower concentration of secondary metabolites compared to the corresponding young leaves. This study reveals that khat leaves and tender stems accumulated a substantial amount of secondary metabolites, particularly tannins.