Abstract: Background and Objective: The waste products of the tamarind canning industry have been discarded; however, it has potential health benefits. Herein, the study was carried out HPLC profiling of phenolic constituents of Tamarindis indica pericarp and seeds. Furthermore, the cytotoxic activity against HUH-7 cells was evaluated and assessed with molecular docking study on angiogenesis-related VEGF kinase proteins in addition to evaluating the level of released VEGF in treated HUH-7 cells by ELISA. Materials and Methods: Folin-ciocalteu and AlCl3 assays were used for quantification of total phenolics (TPC) and total flavonoids (TFC) contents, respectively. Molecular docking study was done on VEGF kinase proteins. Results: TPC and TFC of pericarp and seeds were 0.35±0.02 g GAE g–1 DE and 0.12±0.009 g CE g–1 DE, 0.39±0.01 g GAE g–1 DE and 0.03±0.006 g CE g–1 DE, respectively. In pericarp, 8 phenolics were tentatively identified, where (+)-catechin was the major (27,386.04 μg g–1 DE) followed by gallic acid and naringenin (931.47, 500.42 μg g–1 DE) respectively. While in seeds, 11 phenolics were tentatively identified, where naringenin was the major (95,305.47 μg g–1 DE) followed by (+)-catechin and rutin (54,930.29, 15,361.66 μg g–1 DE) respectively. Aqueous and methanol seeds extracts exhibit cytotoxic effect with IC50 27.4±1.81 and 13.4±0.94 μg mL–1, respectively, it was more potent than aqueous and methanol pericarp extracts which had IC50 132±5.82 and 61.6±3.16 μg mL–1. The tested phenolics were fit on the active sites of VEGF kinase targets with varied degree of interactions. The cytotoxic and anti-angiogenic activities were confirmed in light of phenolics docking interactions. Conclusion: Results demonstrate for the first time that phenolics could inhibit angiogenesis via inhibiting kinase proteins, which could therefore be developed as antiangiogenic drugs.