Hydroethanolic longan (Dimocarpus longan Lour.) leaf extract has reported remarkable biological activities related to the aging process for use in cosmeceuticals. Finding the bioactive chemical marker (BCM) could play a crucial role for cosmeceutical manufacturers in guaranteeing the quality of the extract and its efficacy. This study aimed to select the most potential BCM established and predicted for the anti-aging skin of hydroethanolic longan leaf extract. The assessment of anti-aging of the skin was determined by evaluating in vitro antioxidant activities, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and inhibiting lipid peroxidation assay. Furthermore, anti-hyaluronidase and anti-collagenase activity were also determined. The extract underwent bioassay-guided fractionation using normal phase preparative-thin layer chromatography. Ethyl gallate in the fractionated extract possessed biological activities as a high proportion part. The strong positive linear relationship between DPPH scavenging, lipid peroxidation inhibition, anti-collagenase, and anti-hyaluronidase activity (r = 0.997, 0.972, 0.998, and 0.998, respectively) under the deterioration of the ethyl gallate was shown. The molecular docking of ethyl gallate to collagenase and hyaluronidase resulted in a good and acceptable binding affinity. Therefore, ethyl gallate could be potentially used as a bioactive chemical marker for hydroethanolic longan leaf extract in pharmaceutical and cosmeceutical applications.