Background: The objective of the present study is to evaluate the impact of oral health practice and knowledge level of caregivers on periodontal status of adults special needs in Aseer Region, Saudi Arabia. Methodology: A cross-sectional study was conducted on 180 caregivers and 180 adults with special needs divided into three equal groups (n = 60 + 60 + 60) based on type of disabilities: Visual impairment group (I); moderate mental retardation group (II); and physical impairment group (III). Questionnaire forms were used to assess the oral health practice and knowledge level of caregivers. The clinical examination of special needs adults was done to assess the effect of oral health practice and knowledge level of caregivers on periodontal status of adults special needs. All data were collected and analyzed by the SPSS statistical software and (ANOVA) to assess the variations in the mean and standard deviation (±SD) of clinical findings. Results: Acceptable periodontal, oral health knowledge, awareness and oral health practice were detected among caregivers, particularly, group (II) more than group (III) and group (I). But there were no significant differences in periodontal clinical parameter scores in the comparison between the study groups. Conclusion: It is concluded that the level of oral health practice and knowledge of caregivers included within the current study, were not effective in keeping periodontal health of special needs adults.