In the present work, we have designed and synthesized novel indolyl-4H-chromene-phenylprop-2-en-1-one derivatives (5a–o) using Amberlite SR1L Na (150 mg) as catalyst at 60 °C in DMSO. For the first time, a series of 2-alkoxy-2H-chromen chalcones (3a–h) are prepared by reacting 1-(2-ethoxy-2-methyl-2H-chromen-3yl)ethan-1-one with various substituted aldehydes in the presence of 20% ethanolic sodium hydroxide. After optimizing the reaction conditions, the synthesized chalcones (3a–h) were further reacted with various indoles (4a–b) via regioselective nucleophilic substitution to yield the corresponding derivatives (5a–o) in excellent yields by C[sbnd]C coupling reaction and confirmed by 1H, 13C NMR HRMS and UV–Visible spectroscopy analysis. The employed synthetic route offered several advantages such as simple reaction conditions, easy handling, short reaction time, environmentally benign, and reusability of the catalyst. The synthesized compounds (5a–o) was studied for their solvatochromic property with increasing polarity of solvents. The compounds (5a–o) were evaluated for their antioxidant activity by free radical screening using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Also, their in-vitro antibacterial activity has been investigated against gram positive (S. aureus and B. subtilis) and gram negative bacteria (Klebsiella and E. coli) by agar well technique. Among the compounds employed, 5g and 5h not only showed promising antioxidant activity but also significant antibacterial activity against S. aureus compared to the experimental standards. © 2017 Elsevier B.V.