Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely studied for drug delivery due to their biocompatibility, biodegradability, and tuneable release characteristics. However, conventional synthesis methods often suffer from limited scalability and poor control over physicochemical properties. In this study, a hydrodynamic flow focusing microfluidic platform was applied to synthesise PLGA NPs via nanoprecipitation, enabling precise modulation of formulation parameters. The effects of flow rate ratio (FRR), PLGA concentration, and poly(vinyl alcohol) (PVA) surfactant concentration on NP size, polydispersity index (PDI), and zeta potential were systematically evaluated. Mixing time calculations under varying FRR indicated that lower FRRs promoted faster interfacial mixing; resulting in smaller, more uniform particles. Increasing PLGA concentration produced larger NPs due to viscosity-driven diffusion limitations, while optimising PVA concentration improved mixing efficiency and particle stabilisation, minimising particle size and PDI. Both hydrophilic (rhodamine B) and hydrophobic (curcumin) compounds were successfully encapsulated, confirming the platform’s versatility. This microfluidic approach offers a scalable and reproducible approach for fabricating highquality PLGA NPs; thus supporting their application in targeted and controlled drug delivery.