MoS2 is an intriguing layered material widely used in catalysis, lubrication, optoelectronic devices and many other fields, where various structural defects (e.g., vacancies, edges, dopants) will be created in the synthesis and application processes. The promoting effect of defects on the electrochemical reactions, for example, oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER), on MoS2 has been intensively pursued for efficient catalysts, but should be avoided for durable and superior lubricants and optoelectronic devices working in many atmospheric/aqueous environments. Here, from the perspectives of density-functional-theory simulation, we review the contemporary research progresses on these electrochemical reactions and the underlying microscopic mechanisms of defective MoS2, and finally project the future research trends and challenges on the electrochemical catalysis and corrosion of defective MoS2.