Background Sleep apnea syndrome has gained significant recognition over the last decade as a potential cause of substantial childhood morbidity. This study aimed to evaluate the impact of the Apnea Hypopnea Index (AHI), Respiratory Distress Index (RDI), and Oxygen Desaturation Index (ODI) among adolescents with sleep apnea syndrome. Objectives The objective of this study is to compare the impact of Nadi Shuddhi Pranayama with routine treatment modalities on the AHI, RDI, and ODI among adolescents with sleep apnea syndrome. Specifically, the study aims to evaluate the effectiveness of Nadi Shuddhi Pranayama in improving AHI, RDI, and ODI in this population. Methods This study was an interventional case-control study and enrolled 34 adolescents aged 10 to 18 years who were diagnosed with sleep apnea syndrome. The participants were divided into two groups: the Nadi Shuddhi Pranayama group (n=17) and the control group (n=17). Baseline assessments included the collection of demographic information, medical history, and polysomnography results to determine the AHI, RDI, and ODI. Follow-up assessments were conducted post-intervention to measure changes in the AHI, RDI, and ODI. Results There were no significant differences between groups in terms of age (p = 0.176) or gender distribution (p = 0.300). After the intervention period, participants in the Nadi Shuddhi Pranayama group showed significant improvements in the Apnea Hypopnea Index compared to the standard care group (p = 0.007). However, there were no significant differences in the Respiratory Distress Index (p = 0.547) or Oxygen Desaturation Index (p = 0.304) between the groups post-intervention. Subgroup analysis based on severity categories (Mild, Normal) for the Apnea Hypopnea Index showed a significant difference between the Nadi Shuddhi Pranayama and standard care groups (p = 0.037). However, there were no significant differences in the Respiratory Distress Index (p = 0.300) and Oxygen Desaturation Index (p = 0.169) between the groups in this subgroup. Conclusion These findings suggest that Nadi Shuddhi Pranayama may improve the Apnea Hypopnea Index in adolescents with sleep apnea, particularly in those with mild symptoms, but did not significantly affect the Respiratory Distress Index or Oxygen Desaturation Index., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee issued approval 133/06/2023/IEC/SMCH. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yelkur et al.)