Polyphenols - rich plants can be used to reduce health disorder resulting from cancer and infectious diseases. Methodology: Different solvent extracts of Ceiba insignis leaves were evaluated for their in vitro cytotoxic, antimicrobial, and antioxidant activities, while their chemical profiles were investigated via high‑performance liquid-chromatography (HPLC) fingerprint analyses. Results: Showed that methanol, butanol, and dichloromethane extracts of Ceiba insignis leaves exhibited a moderate cytotoxicity against HepG2 with IC50 values of 98.54, 75.38, 40.71 µg/ml respectiviely, while petroleum ether and water exhibited weak activity with IC50 values of 118.15 and 170.03 µg/ml respectively and very weak activity was recorded with ethyl acetate extract with IC50 value of 924.05µg. Moreover, methanol, dichloromethane, petroleum ether, and ethyl acetate exhibited strong antimicrobial activities with inhibition zones (20-25 mm), (15-30 mm), (14-16 mm), and (16-28 mm) respectively, while butanol and water exhibited low to moderate activity with inhibition zones (0-18 mm), and (0-16 mm) respectively. On the other side, strong DPPH antioxidant scavenging activity was recorded within petroleum ether extract with IC50 (24.72 μg/ml), while the least antioxidant activity was recorded within ethyl acetate with IC50 (97.50 μg/ml). HPLC finger-print analyses revealed the presence of major compounds; syringic acid in dichloromethane extract, gallic acid, chlorogenic acid & syringic acid in ethyl acetate extract, and naringenin & gallic acid in methanol, butanol and water extracts, this finding provides an insight into the usage of the tested species as a source of naturally occurring antioxidant, cytotoxic and antimicrobial agents.