Background: This systematic analysis of case reports aimed to compile available knowledge and identify trends in disorder onset, symptoms, treatment, and possible interventions across individual cases associated with Lesch–Nyhan syndrome (LNS) oral self-injury. Materials and methods: “Lesch–Nyhan syndrome” and “oral self-mutilation” were entered as keywords in four search engines. All cases reporting the patients’ demographics and documented episodes of self-mutilation, with details on treatment and management, were included. Descriptive statistics and a narrative approach were used to present findings. Results: Nineteen case reports comprising 26 patients were included. The patients were reported to develop oral self-mutilation at an average age of 4 ± 3.42 years. The medical history of 69.23% of patients suggests developmental delays. In 53.84% of patients, individuals exhibited ulceration or lacerations across the tongue, lower lip, thumbs, cheeks, index finger, dorsum of hands, and extensor surface of the forearm. Multiple teeth extractions, mouth splints and guards, allopurinol, and botulinum toxin-A were reported as common treatment modalities. Conclusion: A multidimensional strategy and improved genetic elucidation can potentially identify disease genes for the nonelucidated pathophysiology and clinical manifestations of LNS. Clinical significance: Given the challenges faced by clinicians in syndromic patients, the paper tabulates pharmacological and nonpharmacological management with their reported success. These suggestions can potentially guide pediatricians and dentists to formulate a treatment plan for LNS cases.