Background: Oral complications resulting from cancer immunotherapies can inflict pain, disrupt nutrition intake, escalate the cost of care, and significantly undermine the quality of life for cancer patients. However, they are frequently under-researched and overlooked due to the perception that they do not directly contribute to mortality risks among individuals with cancer. This study aimed to assess oral complications among adults with breast cancer who initiated human epidermal growth factor receptor inhibitors (HER2i). Methods: Patients with breast cancer treated with or without HER2i between 2008 and 2023 were included from 92 healthcare organizations across the U.S., and propensity score matched on age, comorbidities, metastatic diseases, and previous antineoplastic treatments. Kaplan-Meier analysis and log-rank tests were used to compare outcomes between the cohorts. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using the Cox proportional hazard regression model. Outcomes of interest included stomatitis, dental caries, and tooth extraction. Results: A total of 15,311 HER2i initiators were matched to 15,311 HER2i non-users with breast cancer. HER2i initiators presented with a significantly higher risk for stomatitis (HR, 3.03; 95% CI, 2.51 to 3.67) and dental caries (HR, 1.49; 95% CI, 1.05 to 2.13). Pertuzumab (HR for stomatitis, 8.81; 95% CI 7.77 to 9.98; HR for caries, 3.94, 95% CI 2.83 to 5.50) and trastuzumab (HR for stomatitis, 3.97, 95% CI 3.59 to 4.38; HR for caries, 2.00, 95% CI 1.57 to 2.54) were both significantly associated with higher risks of dental caries and stomatitis. Pertuzumab use was also associated with a 1.9-fold higher risk of tooth extraction (HR 2.92, 95% CI 1.18 to 7.2). Conclusions: HER2i therapy was associated with a significantly higher risk for stomatitis, dental caries, and tooth extraction in patients with breast cancer. These findings imply that an integrated approach to breast cancer patient care should include oral care and involve oral medicine specialists and dentists.