Background: Allergic diseases are among the most prevalent health issues globally, affecting nearly one-third of the population, according to the World Health Organization. These conditions significantly impact patients’ quality of life and societal productivity. Asthma, in particular, is a leading but preventable cause of death, with approximately 250,000 deaths reported annually. Environmental and genetic factors are major contributors to allergic disease risk. Among the key players in allergic pathophysiology is interleukin-13 (IL-13), which promotes a Th2-skewed immune response and stimulates IgE antibody production. In this context, single nucleotide polymorphisms (SNPs) are of interest due to their role in individual variability in immune responses and disease susceptibility, potentially altering protein structure, expression, or function. Aim: This study aimed to investigate the association between the +2044A>G polymorphism in the IL-13 gene and susceptibility to respiratory allergic diseases in a Syrian population. Methods: A case-control study was conducted, employing clinical diagnostic criteria and skin prick testing (SPT) to confirm allergic status in the case group and rule it out in the control group. Venous blood samples were collected from all participants, and genomic DNA was extracted. The target DNA sequence containing the +2044A>G polymorphism was amplified using polymerase chain reaction (PCR), followed by digestion of the PCR product with the restriction enzyme NlaIV, which recognizes the nucleotide change at the polymorphic site. Genotypes and allele frequencies were determined, and statistical comparisons and analyses were performed using R software. Results: The study encompassed 99 participants: 64 clinically diagnosed patients with respiratory allergic diseases and positive SPT results, and 35 non-allergic individuals serving as controls. Statistically significant differences were found in the distribution of genotypes and alleles between the two groups. The G allele was more frequent among patients than controls, suggesting it may act as a risk factor. Individuals carrying at least one copy of the G allele (AG or GG genotypes) had an approximately 18-fold increased likelihood of developing allergic disease compared to those with the AA genotype (OR = 17.81). Furthermore, individuals homozygous for the G allele (GG genotype) had approximately 4.45 times higher odds of being affected compared to those without the GG genotype (OR = 4.45). All observed differences were statistically significant (p G polymorphism in increasing susceptibility to respiratory allergic diseases. Our results may help pave the way for future advancements in molecular research, diagnosis, and therapeutic strategies targeting such conditions.