Nanofibrillar cellulose (NFC) was extracted by alkaline treatment of Yucca leaves followed by bleaching using H2O2, and then modified by silica nanoparticles (NPs). Obtained silica NPs modified NFC (SiO2 NPs-mNFC) was characterized using FT-IR, XRD, TGA, SEM, TEM and EDX analysis, and its metronidazole drug delivery properties were studied. However bare NFC showed higher loading of metronidazole than SiO2 NPs-mNFC, but NFC showed faster release of metronidazole than SiO2 NPs-mNFC. Release of metronidazole from NFC is not pH dependent, as 92.2% and 85.4% cumulative release percentage of metronidazole was released until 7.5 h, at both pH values of 4.5 and 7.4, respectively. However, SiO2 NPs-mNFC released the metronidazole very slowly, and was also pH sensitive, as cumulative release percentage of metronidazole were measured to be 53.3% at pH = 4.5, and 19.6% at pH = 7.4 after 48 h. Kinetic of the metronidazole release from SiO2 NPs-mNFC was studied by fitting the experimental data with well-known kinetic models, such as First order, Higuchi, Korsmeyer-Peppas, Hixson-Corwell and Baker-Lonsdale models. Results revealed that the metronidazole release is well fitted with Hixson–Crowell models at both pH values, confirming that the change in surface area of SiO2 NPs-mNFC during the process of dissolution has a significant effect on metronidazole release. Fickian diffusion of metronidazole at both pH was concluded by calculating n values of 0.3438 at pH = 7.4 and 0.4224 at pH = 4.5 by nonlinear fitting the release experimental data using Korsmeyer-Peppas model.