External and internal stressors have been found to adversely affect skin health and overall wellness. There is growing interest in the use of anti-inflammatory and antioxidant plant-derived ingredients, such as ashwagandha, saffron, l-theanine, and tocopherol, to mitigate the impact of these stressors. In this study, we evaluate the effectiveness of oral and topical products (InnerCalm and SuperCalm, respectively) that contain naturally derived ingredients on skin redness, skin pigmentation, sleep, and mood in healthy females with Fitzpatrick skin type 1−4 and self-perceived sensitive skin. Subjects were randomized to an oral (oral group), a topical (topical group), or a combination of both the oral and topical interventions (combined group). Standardized photography-based image analysis was used to assess skin redness and pigment. Self-assessments of mood and sleep were measured with the abbreviated profile of mood states (POMS) questionnaire, and the Pittsburgh sleep-quality index (PSQI), respectively. Assessments were made at the baseline, 1-week, 4-weeks, and 8-weeks of the intervention. The average facial redness decreased in the topical group at 8-weeks (p < 0.001) and in the combined group at 4-weeks (p < 0.05) and 8-weeks (p < 0.001), relative to the baseline. The average facial pigmentation decreased in the oral (p < 0.05) and combined (p < 0.05) cohorts at 8-weeks, relative to the baseline. The oral group exhibited an improvement in sleep quality at 1-week relative to the baseline (p < 0.05) and at 8-weeks relative to the baseline (p < 0.05). Finally, the combined group demonstrated improvement in fatigue (p < 0.01) and confusion (p < 0.05) at 8-weeks relative to the baseline, though total mood disturbance increased in all 3 groups over the course of the study. Measured outcomes relating to mood may be confounded with the timing of the study, which ran during the COVID pandemic. Overall, we demonstrate the role of oral and topical herbs and of nutraceuticals for skin health and wellness. Further research will be needed to elucidate synergistic effects in oral and topical combination regimens.