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Objective: There is a need to address the mental health insufficiencies among the home-quarantined COVID-19 patients. Telemedicine is reckoned as a productive means to stay connected with patients during pandemic. This study explores the role of Yoga and Naturopathy Interventions (YNI) as the telemedicine in improving depression, anxiety, stress, quality of life (QoL), and symptom scores among home-quarantined COVID-19 patients. Methods: This was a nonrandomized controlled study that included 112 COVID-19 patients who received either YNI (n?=?56), which includes yoga therapy, naturopathic diet, steam inhalation, self-acupressure delivered across the day or simple sectional breathing (n?=?56) through a telemedicine mode for 14 days, along with standard care. The allocation of the study participants to either YNI or Breathing was done by two of the investigators. At baseline and on the 14th day, the Depression Anxiety Stress Scale (DASS-21), World Health Organization (WHO) QoL, and Symptom scores were measured. Results: A generalized linear model was used to evaluate the effects of intervention on stress, anxiety, depression, and WHO-QOL scores. The YNI group had shown significant improvement in DASS-21 scores and the QoL domains as compared with the controls. The severity of cough was significantly reduced in the study group compared with the controls. However, the changes in the severity of other symptoms such as breathlessness, persistent pain, pressure in the chest, fever, headache, and loss of smell remained insignificant between the groups. Conclusion: YNI-based telemedicine was found effective in reducing depression, anxiety, and stress and improving the QoL in COVID-19 patients. However, limitations such as a small sample size and a lack of randomization warrant large-scale studies to strengthen these findings. Trial Registration: Clinical Trial Registry Number: CTRI/2021/05/033816.