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Natural polymers like gelatin have been used as a potential drug carrier for controlled delivery applications due to their various advantages over synthetic polymers. Cellulose Whiskers (CWs) have the capacity to form strong hydrogen bonds which help in controlling the release of drug and also provide good strength to the drug carrier. In this report, CWs were prepared from filter paper cellulose by acid hydrolysis. Also, attempt was made to prepare gelatin-CWs nanoparticles by desolvation method using an anti-tuberculosis drug, isoniazid and a crosslinker glutaraldehyde (GA). The CWs and gelatin-CWs nanoparticles were characterized by X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The effect of CWs on gelatin nanoparticles over 8-hour period was measured in swelling studies. Efficiency of drug loading and subsequent release of isoniazid in buffer solutions at pH 1.2 (0.1N HCl) and pH 7.4 (phosphate buffer) were studied. Cytotoxicity study showed less toxicity for gelatin-CWs nanoparticles.