1,3–Indanedione pharmacophore become a promising nucleus for researcher because possesses wide ranges of biological activities. Cyclic diketones 1,3-indanedione derivatives have synthesized via Knovevanegal condensation, by condensing different aromatic aldehydes with 2-(aryl methylene )-(1H)-indane-1,3-(2H)-dione 1 in the presence of alcoholic-piperidine as solvent leading to the formation of different C2 substituted 2-benzylidene-1H-indene-1,3(2H)-diones. On reacting diethyl phthalate(DEP) with ethyl acetate using sodium metal catalyst in alcoholic solution and later acid neutralization affords 1,3–Indanedione 1. The newly designed title compounds have been characterized by FTIR, 1NMR, mass spectral data. The in-vitro MABA carried out for their antitubercular activities against Mycobacterium tuberculosis H37Rv strain. MIC values found 4.5µM to 167µM, the results shown compound 1, 10, 11, 12, 15 demonstrated exceptional potential to inhibit M. tuberculosis compared to standard Isoniazid whereas compounds 2,3,4,5,6,7,8 and 14 showed moderate activity and 7, 8 showed less activity as compared to standard INH. Molecular docking studies against 6SQ5 enzyme with compounds 11, 6, 9 and 1 exhibited the highest binding energy of −9.9, 9.6, 9.5, and −9.2 kcal/mol, respectively. PASS prediction identifies various biological functions and ADMET lab 2.0 program to compute the drug physicochemical as well as medicinal properties of various substituted 2-(aryl methylene)-(1H)-indane-l,3-(2H)-diones derivatives.