The primary objective of the present article is to understand how the geometric constraints at the surfactant head affect the lipase activity in the reverse micellar interface. To resolve this issue, surfactants 1-11 were designed and synthesized, and activity was measured in 1-11/water/isooctane/n-hexanol reverse micellar systems at z ([alcohol]/[surfactant]) = 5.6, pH 6.0 (20 mM phosphate), 25 degrees C across a varying range of W-0 ([water]/ [surfactant]) using p-nitrophenylalkanoates as the substrate. It was observed that lipase activity increases from surfactants 1 to 2 with the increment in surface area per molecule (A(min)) because of the substitution by the bulky tert-butyl group at the polar head. However, the activity was found to be similar for 2-5 despite an enhancement in the hydrophilic moieties at the interface. This unchanged lipase activity is presumably due to the comparable surface area of 2 to 5 originating from the rigidity at the surfactant head. Noticeably, the enzyme activity improved from 6-8 with the simultaneous increment of both the hydroxyl group and the flexibility of the headgroup whereas that for 9-11 increased exclusively with the flexibility of the headgroup. The common parameter in both groups of surfactants 6-8 and 9-11 is the flexibility of the headgroup, which possibly enhance A(min) and consequently the lipase activity. Thus, the geometric constraints at the surfactant headgroup play a crucial role in modulating the lipase activity profile probably because of the variation in interfacial area.