Keeping in mind the ascribed repute of Diospyros malabarica (D. malabarica), this investigation was commenced to assess the effect of diverse solvents on extraction yields, phytochemical components and antioxidant capability, and in vitro biological activities of D. malabarica for pharmaceutically active constituents to combat various infections. To screen phytochemicals both qualitatively (flavonoids, terpenoid, saponins, tannins) and quantitatively like total phenolic and flavonoid contents, Diospyros malabarica parts include the following: root, leaves, bark, stem, ripe, and unripe fruit were sequentially extracted with organic solvents such as petroleum ether, dichloromethane, ethyl acetate, ethanol, methanol, and water in increasing order of polarity from less polar to more polar solvents. Furthermore, biological activities such as antibacterial, antifungal, anticancer, antidiabetic, and anti-inflammatory were explored. The results revealed that all the tested solvents displayed a vital role in the extraction yield, the content of phytochemicals, and the studied biological activities. Methanol was found as the best solvent followed by the ethanol for the extraction, representing the highest extraction yield (18.3%), rich diversity of phytochemicals, and the highest total phenolic contents (
602
±
0.001
μ
g
EAG/mg of extract) and total flavonoid contents (
455
±
0.6
μ
g
EQ/mg of extract) in bark extract. Furthermore, methanol bark extract showed high in vitro antibacterial activity (
30.25
mm
±
0.9
), antifungal activity (
18.25
mm
±
0.2
), anticancer activity (48%), antidiabetic activity (68%) and anti-inflammatory activity (62%) followed by ethanol amongst other extracts of D. malabarica. Accordingly, methanol might be as an ideal solvent to get maximum content of phytochemicals, promising antioxidants, and in vitro biological activities from bark extract amongst other extracts of D. malabarica compared to pet ether, ethyl acetate, and dichloromethane and may act as free radical rummager because phytochemical constituents exhibit antioxidant capability. Our findings suggest that phytochemical compounds (flavonoids, tannins, phenols, saponins, and terpenoids) found in the bark extract of D. malabarica may be attributed to evaluate potent anti-inflammatory, anticancer, antidiabetic, antibacterial, and antifungal activities.