Background <p><i>Streptococcus constellatus</i> is recognized for its propensity for aggressive abscess formation; however, its refractory nature in periorbital infections remains underemphasized in the literature. This study aims to present two cases of treatment-resistant periorbital abscesses and delineate a successful multidisciplinary management protocol, complemented by a review of previously reported cases to provide a comprehensive clinical perspective.</p> Case presentation <p>The first case involves a 25-year-old male who presented with a three-day history of a maxillary dental abscess followed by 24&#xa0;h of left periorbital swelling and restricted ocular motility. Orbital magnetic resonance imaging (MRI) confirmed cellulitis with a subperiosteal abscess. Despite initial surgical intervention, persistent purulence necessitated subsequent daily bedside drainage. Cultures identified <i>S. constellatus.</i> Functional and aesthetic outcomes were optimized through the targeted use of 5-fluorouracil (5-FU) to mitigate post-inflammatory fibrosis. The second case describes an 18-year-old autistic male with poor oral hygiene presenting with a two-day history of left periorbital edema. Computed tomography (CT) revealed a 5&#xa0;cm subcutaneous collection. Alongside broad-spectrum intravenous antibiotic therapy, the patient underwent five days of daily drainage and ceftazidime irrigation. Cultures similarly identified S. constellatus, and he achieved full functional and cosmetic recovery.</p> Discussion and conclusions <p><i>S. constellatus</i> can precipitate aggressive, treatment-resistant periorbital abscesses. Early multidisciplinary intervention, including targeted systemic antibiotics, repeated surgical drainage, local antibiotic irrigation, and close collaboration with infectious disease specialists, is essential for achieving optimal clinical outcomes</p>