A series of fatty acid ester and ether derivatives have been chemically synthesised based on carbohydrate and non-carbohydrate polyhydroxylated scaffolds. The synthesised compounds, along with their corresponding fatty acid monoglyceride antimicrobials, were evaluated for antimicrobial activity against Staphylococcus aureus and Escherichia coli. Of the derivatives synthesised, several of the carbohydrate-based compounds have antimicrobial efficacy comparable with commercially available antimicrobials. The results suggest that the nature of the carbohydrate core plays a role in the efficacy of carbohydrate fatty acid derivatives as antimicrobials.