Conventional methods for removing sulfur compounds perform poorly when streams are treated with refractory compounds such as dibenzothiophene (DBT) and its derivatives. Current studies have directed efforts to investigate extractive desulfurization (EDS) using microdevices. Microdevices are units with micrometer-sized channels that enhance the mass and heat transfer phenomena. For EDS in microdevices to be viable, it is essential to choose the appropriate extractor solvent. Among the possibilities, an excellent candidate is polyethylene glycol (PEG). The present work aims to analyze the use of PEG 300 for EDS in microfluidics using hexadecane as a model fuel to emulate diesel. The experiments followed the logic of a fractional experimental design that allowed extractive solvent insights into deep desulfurization. In addition, the mass transfer phenomena involved and the application of the best experimental conditions in a real diesel sample were evaluated. The results obtained with model fuel were able to achieve 99.36% DBT removal with a 1.0 min residence time, a 1:1 volumetric ratio, and three extraction cycles. Furthermore, by applying the best experimental conditions to diesel, the total sulfur concentration decreased from 1646 to 312 ppm, resulting in an extractive efficiency of 81.04%.