This work involves in the synthesis of novel 7-substituted-3-acetyl-Coumarin based Indole derivative compounds. Synthesis involves the reaction between 7- substituted-3-acetyl-coumarin and Indole in the presence of acid catalyst as KHSO4 and ethanol as solvent in reflux medium at 60 °C forms 7- substituted-3-acetyl-coumarin Indole. From UV-Visible spectrum the maximum wavelength observed at 378 nm. From Fourier Transform Infrared Spectroscopy (FTIR), the peak at 3350 cm-1 corresponding to N-H stretching, 1700 cm-1 correspond to Lactone carbonyl group stretching and 1231 cm-1 corresponding to C-N stretching. Further the compounds were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and Liquid Chromatography Mass Spectrometry and were evaluated for in-vitro antioxidant and in-vitro α-amylase inhibitory activities. Compound 5b exhibited the highest half maximal inhibitory concentration (IC50) potency in DPPH (IC₅₀ 6.395 ±0.081 μM) and ABTS (IC₅₀ 6.889 ± 0.118 μM) assays among the series was comparable with the standard reference as ascorbic acid (IC₅₀ 4.241 ± 0.237 μM) and trolox (IC₅₀ 6.469 ± 0.091 μM). The antimicrobial screening results revealed that compound 5b displayed potent and minimum inhibitory activity against all tested bacterial strains, namely Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis, whereas compound 5d showed limited activity towards staphylococcus aureus. These findings highlight the influence of substituent effects on the biological efficacy of coumarin-based indole hybrids.