The physiological homeostasis of the masticatory complex in short-faced patients is too robust to be disintegrated and reconstructed due to the powerful masseter muscle. This study innovatively introduced the botulinum toxin-A (BTX-A) into the field of dental occlusal treatment, providing a novel and minimally invasive therapy perspective for the two major clinical problems in these patients (low treatment efficiency and high rates of complications). In total, 10 adult patients with skeletal low angle seeking occlusal treatment (age: 27.0 ± 6.1 years; 4 males and 6 females) were administered 30–50 U of BTX-A in each masseter muscle and evaluated before and 3 months after injection based on cone-beam computed tomography (CBCT). We found a significant reduction in the thickness of the masseter muscle (MMT) (p < 0.0001). With regards to occlusion, we found a significant increase in the height of the maxillary second molar (U7-PP) (p < 0.05) with significantly flattened occlusal curves (the curve of Spee [COS] (p < 0.01), and the curve of Wilson [COW] (p < 0.05)). Furthermore, the variations in the temporomandibular joint exhibited a significant reduction in the anterior joint space (AJS) (p < 0.05) and superior joint space (SJS) (p < 0.05). In addition, the correlation analysis of the masticatory complex provided the basis for the following multiple regression equation: MMT = 10.08 − 0.11 COW + 2.73 AJS. The findings from our pilot study indicate that BTX-A, as a new adjuvant treatment attempt of occlusal therapy for short-faced patients, can provide a more favorable muscular environment for subsequent occlusal therapy through the adjustment of the biting force and may contribute to the reconstruction of healthier homeostasis of the masticatory complex. However, further research is required to establish the reliability and validity of these findings.