The nanoprecipitation of polymers is of great interest in biological and medicinal applications. Many approaches are available, but few generalized methods can fabricate structurally different biocompatible polymers into nanosized particles with a narrow distribution in a high-throughput manner. We simply integrate a glass slide, capillary, and metal needle into a simple microfluidics device. Herein, a detailed protocol is provided for using the glass capillary and slides to fabricate the microfluidics devices used in this work. To demonstrate the generality of our nanoprecipitation approach and platform, four (semi)natural polymers—acetalated dextran (Ac-DEX), spermine acetalated dextran (Sp-Ac-DEX), poly(lactic-co-glycolic acid) (PLGA), and chitosan—were tested and benchmarked by the polymeric particle size and polydispersity. More importantly, the principal objective was to explore the influence of some key parameters on nanoparticle size due to its importance for a variety of applications. The polymer concentration, the solvent/non-solvent volume rate/ratio, and opening of the inner capillary were varied so as to obtain polymeric nanoparticles (NPs). Dynamic light scattering (DLS), transmission electron microscopy (TEM), and optical microscopy are the main techniques used to evaluate the nanoprecipitation output. It turns out that the concentration of polymer most strongly determines the particle size and distribution, followed by the solvent/non-solvent volume rate/ratio, whereas the opening of the inner capillary shows a minor effect. The obtained NPs were smooth spheres with adjustable particle diameters and polymer-dependent surface potentials, both negative and positive.