Among biodegradable polymers, polylactides (PLAs) have attracted considerable interest because the monomer can be produced from renewable resources. Since their initial degradability strongly affects commercial application fields, it is necessary to manage the degradation properties of PLAs to make them more commercially attractive. To control their degradability, poly(lactide-co-glycolide) (PLGA) copolymers of glycolide and isomer lactides (LAs) were synthesized, and their enzymatic and alkaline degradation rates of PLGA monolayers as functions of glycolide acid (GA) composition were systematically investigated by the Langmuir technique. The results showed that the alkaline and enzymatic degradations of PLGA monolayers were faster than those of l-polylactide (l-PLA), even though proteinase K is selectively effective in the l-lactide (l-LA) unit. Alkaline hydrolysis was strongly affected by their hydrophilicity, while the surface pressure of monolayers for enzymatic degradations was a major factor.