A series of novel 2, 4, 5-trimethoxy Chalcones derivatives of biological interest were prepared by Claisen–Schmidt Condensation reaction. All the new compounds were evaluated for (1a-u) antioxidant (DPPH free radical scavenging activity) and antimicrobial (antifungal and antibacterial) activities against some selected pathogenic bacteria and fungi. Amongst all the 21 compounds screened, compounds 1b and 1o exhibited promising antioxidant activity (68 and 71% inhibition, as against standard BHA, 72 % inhibition ) while compounds 1c, 1d, 1j and 1k exhibited antibacterial and compounds 1c, 1j and 1k exhibited promising antifungal activity (MIC of 10-30 μg/ml). The structure–activity relationship (SAR) for all the above stated activities has also been represented.