Healthy dietary intake and physical activity reduce the risk of non-communicable diseases. This systematic review and meta-analysis aimed to examine the effect of interventions including both nutrition and physical activity provided by nutrition and exercise practitioners for adults in the general population (those without diagnosed disease). The MEDLINE, CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews and SportDiscus databases were searched for randomized controlled trials (RCTs) published from 2010 until April 2021. Outcomes included physical activity, fruit and vegetable intake, waist circumference, percent weight loss, quality of life (QoL) and adverse events. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods were used to synthesize and grade evidence. Meta-analyses were stratified according to participant health status. The database search identified 11,205 articles, and 31 RCTs were included. Interventions increased physical activity amount [standardized mean difference (SMD) (95% CI): 0.25 (0.08, 0.43)] (low certainty evidence); increased vegetable intake [SMD (95% CI): 0.14 (0.05, 0.23)] (moderate certainty evidence); reduced waist circumference [MD (95% CI): −2.16 cm (−2.96, −1.36)] (high certainty evidence); and increased likelihood of achieving 5% weight loss for adults with overweight and obesity [relative risk (95% CI): 2.37 (1.76, 3.19)] (high certainty evidence). Very low and low certainty evidence described little-to-no effect on QoL or adverse events. Nutrition and exercise practitioners play key roles in facilitating positive lifestyle behaviors to reduce cardiometabolic disease risk in adults.