The aim is to design and synthesize 2-methylene-cephalosporin antibiotics for antibacterial activity. 2-Methylene-cephalosporin antibiotics were synthesized with starting material of GCLE via Mannich reaction, enzymolysis, and condensation, etc. The study on antibacterial activity was carried out using micro-dilution to detect min. inhibitory concentrations (MIC) on standard Staphylococcus aureus and standard Bacillus canalis capsulatus. Four novel compounds were synthesized. All the compounds were characterized by 1H-NMR and MS. Preliminary test showed that the compound had good antibacterial activities. Through the preliminary bioactivity test, results showed that antibacterial activities of compound 8a, 8b, and 8d on standard Staphylococcus aureus were the same to those of cefixime and cefdinir, and antibacterial activities of the compound 8a and 8b on standard Bacillus canalis capsulatus were the same to those of cefixime and cefdinir.