Anthocyanins (ANCs) are naturally occurring water-soluble pigments responsible for conferring red, blue, and purple colors to fruits, vegetables, flowers, and grains. Due to their chemical structure, they are highly susceptible to degradation by external factors, such as pH, light, temperature, and oxygen. Naturally acylated anthocyanins have proven to be more stable in response to external factors and exhibit superior biological effects as compared with their non-acylated analogues. Therefore, synthetic acylation represents a viable alternative to make the application of these compounds more suitable for use. Enzyme-mediated synthetic acylation produces derivatives that are highly similar to those obtained through the natural acylation process, with the main difference between these two pathways being the catalytic site of the enzymes involved in the synthesis; acyltransferases catalyze natural acylation, while lipases catalyze synthetic acylation. In both cases, their active sites perform the addition of carbon chains to the hydroxyl groups of anthocyanin glycosyl moieties. Currently, there is no comparative information regarding natural and enzymatically acylated anthocyanins. In this sense, the aim of this review is to compare natural and enzyme-mediated synthetic acylated anthocyanins in terms of chemical stability and pharmacological activity with a focus on inflammation and diabetes.