Despite being a key Malaysian economic contributor, the oil palm industry generates a large quantity of environmental pollutant known as palm oil mill effluent (POME). Therefore, the need to remediate POME has drawn a mounting interest among environmental scientists. This study has pioneered the application of Meyerozyma guilliermondii with accession number (MH 374161) that was isolated indigenously in accessing its potential to degrade POME. This strain was able to treat POME in shake flask experiments under aerobic condition by utilising POME as a sole source of carbon. However, it has also been shown that the addition of suitable carbon and nitrogen sources has significantly improved the degradation potential of M. guilliermondii. The remediation of POME using this strain resulted in a substantial reduction of chemical oxygen demand (COD) of 72%, total nitrogen of 49.2% removal, ammonical nitrogen of 45.1% removal, total organic carbon of 46.6% removal, phosphate of 60.6% removal, and 92.4% removal of oil and grease after 7 days of treatment period. The strain also exhibited an extracellular lipase activity which promotes better wastewater treatment. Additionally, Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) analyses have specifically shown that M. guilliermondii strain can degrade hydrocarbons, fatty acids, and phenolic compounds present in the POME. Ultimately, this study has demonstrated that M. guilliermondii which was isolated indigenously exhibits an excellent degrading ability. Therefore, this strain is suitable to be employed in the remediation of POME, contributing to a safe discharge of the effluent into the environment.