Development of excellent bi-functional electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) remains a key issue for the commercialization of various electrochemical devices such as fuel cells and metal-air batteries. Herein, we report the synthesis and electrocatalytic performance of mesoporous nanostructured spinel-type MFe2O4 (M=Co, Mn, Ni) oxides which can serve as alternative low-cost bi-functional electrocatalysts for ORR/OER. Loaded on XC-72 carbon support, the MFe2O4 spinel oxides show the M-dependent catalytic activities with CoFe2O4 being the most active electrocatalyst followed by MnFe2O4 and NiFe2O4 for ORR. For the OER, however, the activity increases in the order: MnFe2O4 <NiFe2O4 ≈CoFe2O4. Additionally, the CoFe2O4 catalyst shows the smallest overpotential between ORR and OER. Compared with commercial IrO2, the MFe2O4 catalysts reveal comparable OER activities. Furthermore, the MFe2O4 catalysts exhibit much better methanol tolerance and stability than Pt/C. Meanwhile, both electrochemical measurements and density functional theory (DFT) calculations verify that the ORRs on the MFe2O4 catalysts are a direct 4 e− pathway in the alkaline solution, and expound the reason for the excellent methanol tolerance of MFe2O4.