Microglia are crucial for neurodevelopment, and the maintenance of central nervous system functions. Calcium signals in microglia regulate the neuronal plasticity critical for learning, memory, and neuron survival. Growing evidence highlights the pivotal function of calcium channels in microglia, along with their cognate proteins, in modulating oxidative stress, neuroinflammation, and multiple neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this review, we summarized the important role and regulatory mechanism of these critical calcium channels and their associated proteins, highlighting their potential as novel therapeutic targets for neurodegenerative diseases.