A good muscle quality index (MQI) may have an inverse relationship with psychosocial variables of depression, anxiety, and stress in adolescents. Unfortunately, little scientific evidence has related MQI to psychosocial variables in this population. Therefore, this research aimed to determine the relationship between the MQI and psychosocial variables of depression, anxiety, and stress in Chilean adolescents. In this quantitative correlational design study, sixty adolescents participated voluntarily (mean ± standard deviation [SD]: age 15.11 ± 1.78 years). Anthropometric parameters, prehensile strength, MQI, and psychosocial variables were evaluated. The results showed that adolescents with high levels of MQI presented lower levels of depression (7.50 ± 6.06 vs. 10.97 ± 5.94), anxiety (5.64 ± 4.81 vs. 9.66 ± 5.12), and stress (6.79 ± 5.09 vs. 10 ± 5.58), in addition to reported lower abdominal obesity (WtHR, 0.47 ± 0.07 vs. 0.52 ± 0.07) than those with low levels of MQI. The group with high levels of MQI reported a higher prevalence of nonanxiety (81.3%, p = 0.031) and a lower prevalence of abdominal obesity (55.8%, p = 0.023). Likewise, a significant inverse association was evidenced between MQI and depression (β; -6.18, 95% CI; -10.11: -2.25, p = 0.003), anxiety (β; -6.61, 95% CI; -9.83: -3.39, p < 0.001) and stress (β; -4.90, 95% CI; -8.49: -1.32 p = 0.008). In conclusion, the results suggest that high levels of MQI are associated with a higher prevalence of nonanxiety in adolescents and a significant inverse association between MQI and levels of depression, anxiety, and stress.