The effects of long-lasting high concentration coffee and caffeine diets on calcium mobilization in rat hippocampal neurons were studied. Changes in the basal calcium level in the hippocampal neurons of control and experimental rats kept on a coffee or caffeine diet were measured. We also recorded the changes in the Ca2+ transients’ amplitude evoked by membrane depolarization or emptying the Ca2+ depot of the endoplasmic reticulum (ER) induced by caffeine activator of the ryanodine receptors. In rats on a coffee or caffeine diet, the basal Ca2+ level was increased by 7.4% and 11%, respectively, compared to control animals. In these groups, the amplitude of Ca2+ transients increased by 70% and 90%, respectively, of the basal level in response to the membrane depolarization. In the same groups, the amount of Ca2+ released from the ER was increased by two and three times, respectively, compared to the control after activation of ryanodine receptors. We concluded that long-term coffee and caffeine diets in rats cause a significant disruption of the hippocampal neurons’ endoplasmic reticulum function. The diets evoke an increase in Ca2+ concentration in the neurons and an excessive release of Ca2+ in response to excitation. The latter can lead to increased excitability of neurons and their further death from excessive Ca2+ levels.