Candida rugosa lipase (CRL) was encapsulated within a chemically inert sol–gel support prepared by polycondensation with tetraethoxysilane (TEOS) and octyltriethoxysilane (OTES) in the presence of N-methylglucamine based calix[4]arene magnetic nanoparticles. The results indicate that the magnetic calix[4]arene based encapsulated lipase particularly has shown high conversion and enantioselectivity. It has also been noticed that the magnetic calix[4]arene based encapsulated lipase has excellent enantioselectivity (E = 460) as compared to the free enzyme (E = 166) with an ee value of >98% for S-Naproxen.