Given the availability of molecular tools, population studies increasingly include the gen-diet interactions in their considerations. The use of these interactions allows for the obtaining of more uniform research groups. In practice, this translates into the possibility of reducing the size of the research group while maintaining the precision of the research. The research results obtained in this way can be used to select certain ingredients and foods in a dietary intervention with a higher degree of personalisation. In both prophylaxis and dietary therapy of overweight and obesity, the proper selection of bioactive ingredients best suited to the given group of consumers is of key importance. Hence, the aim of the presented study was to assess the effectiveness of a dietary intervention with the use of lactoferrin (LF)-fortified yoghurt, in terms of the ability to regulate body weight and carbohydrate metabolism in individuals whose genomes contained single nucleotide polymorphisms that predisposed them to increased accumulation of fatty tissue and consequently overweight or obesity. A group of 137 participants (98 women and 37 men) of Polish origin were screened for the presence of four single nucleotide polymorphisms (rs993960—FTO gene, rs7903146—TCF7L2 gene, rs10830963—MTNR1B gene, and rs1121980—FTO gene). Subsequently, a group of 19 participants diagnosed with the presence of risk factors within said SNPs underwent a 21-day dietary intervention (crossover study) with the use of yoghurt fortified with lactoferrin (200 mg/day). The results of the study revealed a genetic difference between the Polish population and the European average, in terms of the SNPs analysed. The dietary intervention showed a statistically significantly higher efficiency in terms of body mass reduction (p = 0.000) and lowering the glycated haemoglobin ratio (HbA1c) (p = 0.000) when consuming specially prepared yoghurt containing lactoferrin, as compared to results registered for unfortified yoghurt. Given the above, yoghurt fortified with LF should be considered as a viable element of diet therapy in overweight and obese patients diagnosed with risk factors within the analysed polymorphisms.