Background: Autism spectrum disorder (ASD) and Down syndrome are among the most common neurodevelopmental conditions encountered in pediatric dentistry patients, yet direct comparative data on their oral health profiles remain scarce. This study compared caregiver-reported oral health problems, home oral hygiene difficulties, and barriers to dental care access among individuals with ASD versus Down syndrome. Methods: This study was conducted between March and June 2025 in five specialized educational institutions and Non-Governmental Organizations (NGOs) in Oradea, Romania. A structured 15-item questionnaire was administered to caregivers of individuals with ASD (n = 55) or Down syndrome (n = 22). Data were analyzed using Fisher’s exact test and the Mann-Whitney U test (with statistical significance set at p < 0.05). Results: Dentist-diagnosed dental problems were more prevalent in the ASD group (90.90% vs. 68.18%, p = 0.031, Odds Ratio (OR) = 4.67, 95%Confidence Interval (CI) 1.29–16.87), as were tooth/jaw pain (72.72% vs. 40.90%, p = 0.010, OR = 3.85), parafunctional oral habits (72.72% vs. 45.45%, p = 0.034, OR = 3.20), and sensitivity to oral touching/cleaning (63.64% vs. 36.36%, p = 0.042, OR = 3.06). Cooperation difficulties during dental visits were more common in the ASD group (70.91% vs. 36.36%, p = 0.005, OR = 4.08), and most ASD caregivers reported visiting the dentist only when a problem arose (65.45% vs. 13.64%, p < 0.001). Difficulties ensuring correct toothbrushing were greater in the Down syndrome group (45.45% vs. 9.09%, p = 0.001, OR = 7.71). Conclusions: These findings suggest that ASD and Down syndrome are associated with differing oral health profiles. Given the largely unadjusted nature of the comparisons and the small sample size, the results should be regarded as hypothesis-generating, pending confirmation in larger, multivariable-adjusted studies.