The peel of key lime is regarded as a byproduct that contains a substantial amount of bioactive components, including essential oil. The extraction of essential oils from key lime peel typically involves conventional techniques such as hydro-distillation or solvent extraction, which are known for their time-intensive and energy-intensive. The employing of microwave pretreatment has emerged as a conventional approach in the extraction of essential oils from various plant materials. The objective of this study was to investigate the optimization of the effect of microwave pretreatment method on essential oil of key lime peel. Response surface methodology based on Face-Centered CCD was applied to optimize the parameters for microwave pretreatment such as microwave power (600 – 800 W), irradiation time (2 – 5 min) and solid-to-solvent ratio (SSR) (1:0 – 1:2 w/v) . The essential oil extracts at optimized microwave pretreatment conditions were compared with hydro-distillation. The optimized condition of microwave pretreatment was 1000 W microwave power, 2 min irradiation time and SSR of 1:0 w/v. The analysis of ANOVA and three-dimensional response surface revealed the primary factor of microwave pretreatment conditions that affects the yield of essential oil was the SSR, follow up by irradiation time and microwave power. The essential oil was subjected to analysis using GC-MS, revealing the presence of 39 compounds in both the essential oils obtained from pretreatment and non-pretreatment using microwave. No discernible disparities were observed in the composition of essential oil under all of those conditions.