A modest 5-10% reduction in body weight in individuals with overweight or obesity can meaningfully improve cardiometabolic health (1). Lifestyle interventions, combining a reduced-calorie diet with physical activity remain foundational for weight management, but often limited by poor long-term adherence (2). Alternatively, pharmacological therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists, can be effective but are constrained by adverse effects, costs, and weight regain after discontinuation (3). Hence, phytochemical-rich plants with anorexigenic properties may offer a complementary dietary approach, influencing appetite, satiety and energy intake to support long-term weight management and reduce cardiovascular risk. The appetite-modulating effects of several phytochemical-rich plant extracts, bitter melon (Momordica charantia), gurmar (Gymnema sylvestre), hops (Humulus lupulus), and Caralluma (Caralluma fimbriata) were investigated through three studies: (i) a systematic review (SLR) to synthesise the existing evidence; (ii) an in vitro human colorectal NCI-H716 cell model to assess active GLP-1 secretion; and (iii) a randomised, double-blinded, placebo-controlled crossover trial in individuals with overweight and obesity to assess acute subjective appetite using visual analogue scales and ad libitum food intake (n = 31). The SLR revealed that M. charantia’s effects on appetite including hormonal, subjective and food intake remain rarely explored; G. sylvestre altered sweet taste perception and led to reduced sugar intake; H. lupulus acutely suppressed appetite, evidenced by reduced energy intake and improved satiety-related biomarkers in normal-weight adults; and C. fimbriata effectively regulated appetite with longer-term administration, via reduced food intake and anthropometric outcomes, along with improved satiety biomarker profile. In vitro, M. charantia (1000 µg/mL), G. sylvestre (350 and 500 µg/mL), and C. fimbriata (750 and 1000 µg/mL) significantly stimulated active GLP-1 secretion (p < 0.05) compared to vehicle control (2.56 ± 0.72 pg/µg protein), with the strongest response at G. sylvestre 500 µg/mL (8.22 ± 2.45 pg/µg protein), suggesting a dose-dependent potential to enhance satiety and reduce food intake. Nevertheless, capsules containing a single 500 mg dose of each plant extract did not translate to reduced acute ad libitum energy intake and subjective appetite ratings following a standardised breakfast meal in humans. Collectively, these studies indicated modest appetite-regulating effects across these plant extracts. Physiologically relevant doses that increased active GLP-1 in vitro did not acutely suppress subjective appetite in overweight/obese participants, possibly reflecting insufficient dosing to elicit endogenous GLP-1 release, or a method of administration not suitable for detecting measurable appetite responses. Appetite regulation reflects a complex interplay of physiological, hormonal, and social influences, which may not be fully captured by in vitro GLP-1 assays or by energy intake and subjective appetite measures alone. Future research should prioritise longer-term investigation incorporating physiological appetite markers, gastric emptying, and objective measures of energy intake.