<p>To improve the water resistance of products prepared from water-soluble cellulose derivatives, we prepared cellulose-based nanoparticles without chemical modifications such as crosslinking. We employed a W/O (water-in-oil) miniemulsion as a nanoreactor to prepare cellulose-based particles. Methylcellulose (MC) was selected as the cellulose-derived biomass polymer. Aqueous nanodroplets, including MC, were suspended in corn oil by homogenization and ultrasonication. MC hydrogel nanoparticles (MC-H) were subsequently obtained via the gelation of MC within the nanodroplets with increasing temperature. Next, to obtain MC xerogel nanoparticles (MC-X), we carried out water evaporation from MC-H. Furthermore, MC-X with different inner structures could be obtained by tuning the temperature and pressure of the evaporation conditions. MC-H and MC-X showed high water resistance because of the strong association of MC chains, which was promoted in confined vessels such as nanodroplets and nanoparticles. In addition, the release of water-soluble substances from MC-H was promoted at 4 °C below the dissolution temperature of MC, whereas MC-X exhibited suppressed release because of the strong association of MC chains. To explore the utility of MC-X as a biomass-derived filler, it was embedded in the polymer film. MC-X was slightly aggregated but evenly distributed within the film without compromising its transparency.</p>