Aim: The present study aimed to assess the efficacy of a nutraceutical ingredient, SelectSIEVE® Rainbow, based on botanical extracts, in ameliorating cellulite-derived skin imperfections and microcirculation. The nutritional supplement contained a mixture of Oryza sativa (L.), Citrus sinensis (L.) Osbeck, Ananas comosus (L.) Merr, and Actinidia chinensis Planch; all ingredients were botanicals that can be used in food supplements. Results: In vitro studies showed the high capacity of the supplement to have an anti-inflammatory, antioxidant, and hypolipidemic effect, accompanied by an interesting proteolytic activity. The randomized double-blind placebo-controlled clinical trial, carried out on 60 women during an 8-week treatment period, confirmed the in vitro study results. SelectSIEVE® Rainbow showed a whole-body shaping activity, with a reduction of the waist, hip, and tight circumference of 0.8, 0.65 and 0.72 cm, respectively. It also showed a reduction of subcutaneous fat mass of 1.24 mm and body weight, with an average of 0.7 kg and positive peaks of −2.9 kg. Skin health and appearance were also improved: +5.4% skin elasticity, +5.5% skin tonicity and +5.7% skin draining. Finally, the dermatological evaluation of the cellulite score and microcirculation showed an improvement in 57% and 60% of the subjects enrolled in the studies. Conclusions: This first study provides interesting inputs on the effectiveness of the nutraceutical complex standardized in polyphenols, anthocyanins and proteolytic enzymes to counteract cellulite blemishes and improve local microcirculation. The positive response encourages deeper studies and further investigation.