Heliotropium strigosum plant is widely used in traditional medicines for treatment of various ailments. In current study, an effort was made to evaluate phenolic profile as well as antidiabetic and antioxidant activities of crude methanol extract and different solvent (n-hexane, ethyl acetate, chloroform and aqueous) fractions of H. strigosum. Total phenolic contents were determined by spectrophotometric assay. Polyphenolic compounds in crude methanol extract and each solvent fraction were identified by reverse phase high performance liquid chromatography (RP-HPLC). Antioxidant and antidiabetic activities were determined using DPPH and α-amylase inhibition assays, respectively. The outcome of spectrophotometric assay showed that methanol extract had higher amount of total phenolic (84.50 ± 0.06 μg GAE/ mg of plant extract) contents than aqueous, ethyl acetate, chloroform and n-hexane fractions, respectively. The RP-HPLC analysis revealed the maximum number of phenolic (chromotropic acid, quercetin, trans-4-hydroxy-3-methoxy cinnamic acid, vanillic acid, gallic acid, caffeic acid, m-coumaric acid, p-coumaric acid, syringic acid, sinapic acid and ferulic acid) compounds in methanol extract. Methanol extract (IC50 = 8.97 μg/mL) exhibited the maximum antidiabetic activity followed by aqueous (IC50 = 20.04 μg/mL), ethyl acetate (IC50 = 27.79 μg/mL), chloroform (IC50 = 56.87 μg/mL) and hexane (IC50 = 32.16 μg/mL) fractions, respectively. The outcome of antioxidant assay revealed that methanol extract was the leading one with regard to antioxidant activity at different doses (10 to 250 μg/mL). The current study concludes that H. strigosum solvents extracts with significant phenolic profile and potent biological activities could be explored for potential uses in neutraceutical and pharmaceutical industries.