Andrographis paniculata, a popular immune-boosting supplement, faces quality concerns due to potential adulteration and reliance on single-marker quality assurance. To address these, a comprehensive UHPLC-PDA and LC-QToF-MS method was developed and validated to quantify and identify three classes of compounds: phenolic acids, diterpenoid lactones (including their glycosides), and flavonoid glycosides. The method achieved LOD of 10300 ng/mL and LOQ of 251000 ng/mL for fourteen reference standards. Analysis of plant samples revealed total phenolic acids (1-4; 0.3-13 mg/g), flavonoid glycosides (6, 10, and 11; 0.2-2 mg/g), diterpene lactones (7, 13, and 14; 1.4-31 mg/g), and diterpene lactone glycosides (5, 8, 9, and 12; 0.6-17 mg/g). Furthermore, over 100 phytochemicals were tentatively identified based on characteristic mass spectral features in A. paniculata. Applying this comprehensive phytochemical profile to various supplement products revealed that over 25 % of commercial A. paniculata products failed to meet pharmacopeia standards. Detailed analysis demonstrated significant variations in the plant-part-specific distribution of diterpene lactone and its glycosides, as well as flavonoid glycosides. Some products exhibited elevated mean values for these three analyte groups, while others showed significantly lower values contributing to the observed failures. Moreover, the analytical data revealed a significant discrepancy in andrographolide (7) content, a standard quality assurance marker, between plant materials (0.4-23 mg/g) and dietary supplements (0-278 mg/serving size). Specifically, a 13 % andrographolide decrease and a corresponding increase in 14-deoxy-11,12-didehydroandrographolide (14) in A. paniculata capsules suggest processing-induced dehydration, necessitating optimized production to maintain biologically active andrographolide content. These findings underscore the necessity for rigorous quality control and comprehensive analytical methods to ensure the quality assurance of A. paniculata supplements.