Abstract: The PICOSEC Micromegas (MM) is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure. It features a two-stage amplification process that leads to a significant deterioration of non-uniformity when scaling up to larger areas. Since the performance of gaseous detectors is highly dependent on the choice of working gas, optimizing the gas mixture offers a promising solution to improve the uniformity performance. This paper addresses these challenges through a combined approach of simulation based on Garfield++ and experimental studies. The simulation investigates the properties of different mixing fractions of gas mixtures and their impact on detector performance, including gain uniformity and time resolution. To verify the simulation results, experimental tests were conducted using a multi-channel PICOSEC MM prototype with different gas mixtures. The experimental results are consistent with the findings of the simulation, indicating that a higher concentration of neon significantly improves the detector’s gain uniformity. Furthermore, the influence of gas mixtures on time resolution was explored as a critical performance indicator. The study presented in this paper offers valuable insights for improving uniformity in large-area PICOSEC MM detectors and optimizing overall performance.