We developed a mathematical model to simulate the dynamics of background synaptic noise in non-neuronal cells. By employing the stochastic Ornstein–Uhlenbeck process, we represented excitatory synaptic conductance and integrated it into a whole-cell model to generate spontaneous and evoke cellular electrical activities. This single-cell model encompasses numerous biophysically detailed ion channels, depicted by a set of ordinary differential equations in Hodgkin–Huxley and Markov formalisms. Consequently, this approach effectively induced irregular spontaneous depolarizations (SDs) and spontaneous action potentials (sAPs), resembling electrical activity observed in vitro. The input resistance decreased significantly, while the firing rate of spontaneous action potentials increased. Moreover, alterations in the ability to reach the action potential threshold were observed. Background synaptic activity can modify the input/output characteristics of non-neuronal excitatory cells. Hence, suppressing these baseline activities could aid in identifying new pharmaceutical targets for various clinical diseases.