The hippocampus, necessary for the formation of new memories, undergoes experience-dependent synaptic plasticity. These Hebbian changes require synaptic homeostatic compensation to maintain the stability of neuronal systems. While functional and structural modifications have been demonstrated in cortical regions, little is known about how homeostasis affects the long-term structural stability of excitatory synapses in the hippocampus of live mammals. To answer these questions, we employed in vivo 2-photon imaging in mice to track long-term structural dynamics of dendritic spines (as a proxy for excitatory synapses) on pyramidal neurons of the hippocampal CA1 region, under the condition of chronic over-inhibition. To induce over-inhibition of neuronal activity, we chemogenetically activated hDlx-expressing inhibitory neurons in the dorsal CA1. We then analyzed the changes in size and stability of dendritic spines in response to a five-day over-inhibition. We found that a sharp decrease in spinogenesis and an increase in spine loss led to an acute reduction of spine density on the first day of over-inhibition. This effect of over-inhibition was temporary and it recovered within the third day of over-inhibition. Simultaneously, spine sizes stabilized only on the first day of over-inhibition, perhaps to compensate for the acute spine loss and decrease in spinogenesis. Finally, spine density increased when over-inhibition ceased, possibly to compensate for the changes due to over-inhibition. Overall, we show changes in synaptic density, size, and structural dynamics that - we hypothesize - constitute adaptive mechanisms in response to prolonged inhibition of neuronal activity in the hippocampus of live mice.