Intermittent energy restriction (IER) works as an alternative for weight loss considering the difficulty in long-term adherence to continuous energy restriction (CER). To investigate the effects of 2-weeks of 5 days normal diet, 2 days restricted diet (5:2 IER) compared to CER on basal and postprandial metabolism, a two-week randomized parallel trial was conducted in 16 healthy normal-weight participants (aged 20-35). Participants were randomly assigned to either the CER of 20% restriction below estimated requirements 7 days/week or the 5:2 IER, with 70% restriction delivered for two non-consecutive days/week with no restriction on the other 5 days/week. Weight, anthropometry, resting energy expenditure, diabetes and cardiovascular disease risk markers, appetite regulation 3 hours after the test drink and energy intake in an ad libitum test meal were assessed pre- and post- intervention. Weight loss was similar among participants in both groups, mean ± SEM body weight for 5:2 IER fell from 63.1 ± 4.9 to 60.9 ± 4.7 kg vs. 66.1 ± 4.0 to 63.9 ± 3.9 kg for CER (p = 0.61). Both groups experienced comparable reductions in waist and hip circumferences. There was a significant treatment-by-time interaction between 5:2 IER and CER diets for fasting blood glucose (p < 0.05), which were significantly lower after the 5:2 IER diet than after the CER diet (p < 0.01). The fasting blood glucose concentrations fell significantly after the 5:2 IER diet (p < 0.01), from 4.4 ± 0.1 to 4.1 ± 0.1 mmol/L, compared to no changes after the CER diet. There was a significant interaction between the 5:2 IER and CER diets for resting heart rate (p < 0.05), which fell with the 5:2 IER diet from 68 ± 2 to 62 ± 2 BPM, compared to no changes in the CER diet. There were significant interactions between diet patterns for fasting subjective hunger, satiety, fullness, desire to eat and prospective food consumption ratings (p < 0.001, p < 0.01, p < 0.01, p < 0.05 and p < 0.001, respectively). After the 5:2 IER diet, the fasting ratings of subjective hunger, desire to eat and prospective food consumption were observed to decrease, and subjective satiety and fullness were observed to increase. Opposite responses were found for all fasting ratings after the CER diet. The responses for hunger and satiety for the 1-h postprandial ad libitum test meal period showed significant interactions between the diets (p < 0.05 for both). These findings suggest that 5:2 IER would be as effective as CER in decreasing body weight and may also lead to a similar or better improvement of metabolic disease risk markers, and to changes in subjective appetite and satiety ratings which may help to reduce the desire to eat. 5:2 IER may offer a suitable approach to weight reduction for individuals who find CER difficult to follow.