Grape pomace is a by-product that contains high amounts of phytochemicals such as phenolic acids, flavonoids, and anthocyanins. For the efficient extraction of these compounds, extraction optimization was done in the present study. Glycerol concentration, a cheap, non-toxic and abundant green solvent, and liquid–solid ratio were evaluated as the independent factor of the optimization and total phenolic content, total flavonoid content, free radical scavenging activity, total monomeric anthocyanin content, total proanthocyanidin content and ascorbic acid content was analyzed as responses. The result showed that glycerol concentration significantly affected all responses and increasing the concentration resulted in higher extraction of the phytochemicals. Additionally, liquid–solid ratio affected total phenolic content, total flavonoid content, total proanthocyanidin content and ascorbic acid content of the extracts. Glycerol concentration of 50% (w/v) and liquid–solid ratio of 22.4 was determined to be optimum condition to maximize all responses. The optimum conditions were experimentally validated. Overall, the study showed that homogenizer assisted extraction using glycerol as a green solvent is a good method for extraction of phytochemicals from food processing by-products.