Background/Objectives: Cardiovascular diseases remain a leading cause of mortality and morbidity, and dyslipidaemia is one of the major risk factors. The widespread use of herbs and medicinal plants in traditional medicine has garnered increasing recognition as a valuable resource for increasing wellness and reducing the onset of disease. Several epidemiologic and clinical studies have shown that altering blood lipid profiles and maintaining gut homeostasis may protect against cardiovascular diseases. Methods: A randomised, active-controlled parallel human clinical trial (n = 52) with three herbal tea infusions (green (Camellia sinensis) tea with rhubarb root, green tea with senna, and active control green tea) daily for 21 days in a free-living healthy adult cohort was conducted to assess the potential for health benefits in terms of plasma lipids and gut health. Paired plasma samples were analysed using Afinion lipid panels (total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, and non-HDL cholesterol) and paired stool samples were analysed using 16S rRNA amplicon sequencing to determine bacterial diversity within the gut microbiome. Results: Among participants providing fasting blood samples before and after the intervention (n = 47), consumption of herbal rhubarb root tea and green tea significantly lowered total cholesterol, LDL-cholesterol, and non-HDL cholesterol (p < 0.05) in plasma after 21 days of daily consumption when compared with concentrations before the intervention. No significant change was observed in the senna tea group. In participants providing stool samples (n = 48), no significant differences in overall microbial composition were observed between pre- and post-intervention, even at the genus level. While no significant changes in overall microbial composition were observed, specific bacterial genera, such as Dorea spp., showed correlations with LDL cholesterol concentrations, suggesting potential microbiota-mediated effects of tea consumption. Diet and BMI was maintained in each of the three groups before and after the trial. Conclusions: It was found that drinking a cup of rhubarb root herbal or green tea infusion for 21 days produced beneficial effects on lipid profiles and maintained gut eubiosis without observable adverse effects in a healthy human cohort. More studies are needed to fully understand the effects of rhubarb root and green tea in fatty acid metabolism and gut microbial composition
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