A series of 2, 6-dimethoxyphenyl chalcones have been synthesized by Crossed-Aldol condensation of 2, 6-dimethoxyacetophenone and substituted benzaldehydes. The purities of these chalcones have been checked by their physical constants, UV, IR, and NMR spectral data. The spectral data of these chalcones have been correlated with Hammett substituents constants, F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effect of substituents on the spectral group frequencies has been discussed. The anti-microbial activities of these chalcones have been evaluated using Bauer-Kirby disc diffusion method.