Introduction Trigeminal neuralgia (TN) is a chronic condition characterized by sudden, short episodes of excruciating facial pain affecting one or more branches of the trigeminal nerve (V), which severely impacts patients' quality of life. Despite the availability of various treatment options, some cases experience poor pain control. Sphenopalatine ganglion (SPG) block using the Tx360 nasal applicator has recently been introduced with promising results as a treatment option in such cases. Materials and methods Fifteen adult patients of both sexes suffering from classical or atypical TN involving the maxillary (V2) or mandibular (V3) branches, either partially or completely drug-resistant, with a Numerical Rating Scale (NRS) score of 8-9 despite drug treatment, were enrolled in the study. For six weeks, every seven days, they underwent bilateral SPG block with the Tx360 device (Tian Medical Inc., Lombard, Illinois), receiving 0.3 cc of 2% lidocaine in each block. During the subsequent twelve weeks, patients were followed up monthly, and data regarding TN-related pain symptoms were collected using the verbal rating scale and the Short Form-36 (SF-36) Quality of Life Questionnaire. Results All participants exhibited a continuous and significant decrease in NRS scores at each visit during the first six weeks and up to one month after the final SPG block. Subsequently, NRS scores remained stable over the following two months. Significant improvements were noted in all patients in physical functioning, role limitations due to physical health, energy/fatigue, emotional well-being, pain, and general health, as assessed through the SF-36. Discussion Our results align with studies of a similar design demonstrating favorable effects of SPG block in various types of head and neck pain, including TN. Conclusion Repetitive SPG block with 2% lidocaine administered via the Tx360 device resulted in clinical improvement, significantly reducing NRS scores for a three-month period in patients with TN when used as an add-on to standard treatment. This treatment technique was simple, effective, and not associated with significant adverse effects.