Abstract Microdroplets generated using microfluidic techniques offer significant advantages over those generated using conventional methods, including high accuracy and excellent monodispersity. However, there remains a paucity of literature regarding the influence of fluid operating conditions and physical properties on droplet generation, specifically in relation to size and frequency, using computational fluid dynamics (CFD) techniques. In this study, we present a simplified microfluidic chip capable of flexibly adjusting the structure and size of the microchannels based on specific requirements. Subsequently, three-dimensional numerical simulations of this chip were conducted using CFD techniques and fitted a dimensionless model to estimate the droplet generation size and frequency through multivariate nonlinear regression methods. The experimental validation results demonstrated a strong correlation between the fitted data and the experimental observations, with size differences not exceeding 8% and good monodispersity, indicated by a coefficient of variation of less than 2.4%. This study provides valuable insights and a reference for future research.