Parathyroid hormone (PTH), vitamin D and serum calcium play a key role in several physiological and pathological conditions. Vitamin D and PTH receptors are largely expressed in the central nervous system and are involved in the modulation of inflammatory responses. Few studies investigated the association between calcium homeostasis imbalance and psychiatric disorders. This study aims to assess calcium homeostasis imbalance in patients with bipolar disorder (BD) and its impact on clinical outcome. We recruited 199 patients with BD, who were administered with validated assessment instruments to investigate depressive, manic and anxiety symptoms, affective temperaments, childhood trauma and global functioning. Serum calcium, vitamin D and PTH levels were assessed in all patients. Levels of PTH correlated with several clinical characteristics, including the diagnosis of bipolar disorder type I (BD-I), the presence of psychotic symptoms, lithium treatment, suicidality, total number of acute episodes and of hospitalizations (p < 0.0001) and seasonality (p < 0.05). At the regression analyses, higher levels of PTH were predicted by early age at onset, number of hospitalizations, aggressive behaviors (p < 0.05), higher Childhood Trauma Questionnaire total score (CTQ) (p < 0.001) and treatment with lithium (p = 0.01). Our findings suggest that the calcium homeostasis could play a role in BD patients, and that PTH levels are correlated with the clinical severity of the disorder.