This research explored the differences in catalytic activity between MgO and CaO in the transesterification reactions through the combinations of theoretical and experimental studies. A series of transesterification reactions involved cyclic carbonates, straight-chain carbonates, carboxylates, or oxalates was designed systematically. And the results showed that both CaO and MgO exhibited catalytic activity in the transesterification reactions between cyclic carbonates and alcohols, whereas CaO demonstrated superior initial activity when reacting with methanol. In addition, the catalytic efficiency of MgO relatively improved with the increased alcohol chains, such as ethanol and n-butanol. The catalytic efficiency for straight-chain carbonate transesterifications was generally lower compared to cyclic ones over both CaO and MgO. When the carbonates reacted with polyols (such as ethylene glycol), the product selectivity decreased over time, possibly due to the ring-opening reactions between the formed cyclic carbonates and excess ethylene glycol.