Triblock poloxamer copolymer (PM) has been extensively utilized to deliver various ophthalmic pharmaceutical compounds. The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs. In this pursuit, the influence of cellulose nanocrystals (CNC) on the in situ gelation behavior of PM and in vitro release of pilocarpine hydrochloride from the nanocomposites formulations was studied. The critical concentration of gelation of PM being 18% (wt/v) was dropped to 16.6% (wt/v) by the addition of a very low percentage of CNC. The reinforcing nature of CNC via H-bonding in the in situ nanocomposite gel also led to an increase in gel strength along with the sustained release of loaded drugs when compared with the pure PM gel. All formulations revealed that the drug release mechanism is controlled by the Fickian diffusion. Thus, the CNC has a significant effect on the gelation behavior, gel strength, and drug release kinetics of PM-CNC formulations.