Objectives: The aim of this study was to assess the prevalence of oral mucosal lesions (OMLs) and dental caries and to evaluate oral health practices among institutionalized orphan-children in Sana′a city, Yemen. Subjects and Methods: A sample of 202 institutionalized male-orphan-children in the main orphanage in Sana′a city, were matched to 202 non-orphan schoolchildren. Clinical examination included assessment of OMLs based on standard international diagnostic criteria and evaluation of dental status using the Decayed/decayed, Missed/missed and Filled/filled (DMFT/dmft) index according to World Health Organization recommendations. Demographic data and oral hygiene practices were obtained by interviewing each subject using special questionnaire form. Results: Majority of children were in the 12-15 year age group. Nine types of lesions were reported among orphans; the most common lesions were fissured tongue (24.3%), herpes labialis (7.9%) and traumatic ulcers (2.5%). The occurrence of herpes labialis was found to be significantly higher in orphans than in controls (P < 0.01). The prevalence of dental caries was insignificantly lower among the orphans (84.7%) compared with the non-orphans (89.61%; P = 0.136). The mean dmft score was significantly lower in orphans than in controls (2.28 vs. 3.82; P = 0.001). Conclusions: The institutionalized children in this orphanage had a high prevalence of OMLs but low prevalence of dental caries, though they revealed poor oral hygiene practices. Effective oral health promotion strategies need to be implemented to improve the oral health and oral health practices of children living in orphanages.