Astrocytes establish dynamic interactions with surrounding neurons and synchronize neuronal networks within a specific range. However, these reciprocal astrocyte-neuronal interactions are selectively disrupted in epilepsy and Alzheimer's disease (AD), which contributes to the initiation and progression of network hypersynchrony. Deciphering how disrupted astrocyte-neuronal signaling reshapes brain activity is crucial to prevent subclinical epileptiform activity in epilepsy and AD. In this review, we provide an overview of the diverse astrocyte-neuronal crosstalk in maintaining of network activity via homeostatic control of extracellular ions and transmitters, synapse formation and elimination. More importantly, since AD and epilepsy share the common symptoms of neuronal hyperexcitability and astrogliosis, we then explore the crosstalk between astrocytes and neurons in the context of epilepsy and AD and discuss how these disrupted interactions reshape brain activity in pathological conditions. Collectively, this review sheds light on how disrupted astrocyte-neuronal signaling reshapes brain activity in epilepsy and AD, and highlights that modifying astrocyte-neuronal signaling could be a therapeutic approach to prevent epileptiform activity in AD.