Background: Single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL13) gene are associated with vulnerability to allergic diseases, such as asthma and allergic conjunctivitis (AC). Periostin, as an IL13-induced protein, has emerged as a novel biomarker in several allergic diseases. Data among Egyptian patients are still scarce. Aim: To find out the association of IL13 rs20541 gene polymorphism and serum levels of periostin with asthma and AC among Egyptian patients. Patients and Methods: Eighty-one Egyptian allergic patients with asthma, AC, and both asthma and AC (27 each), were enrolled in this case–control study. Twenty-seven age and gender-matched healthy volunteers served as controls. All participants were tested for IL13 rs20541 SNP by real-time polymerase chain reaction, TaqMan method. Serum levels of periostin and IL13 were assessed by ELISA. Results: Compared to healthy subjects, asthmatic patients had a higher frequency of the homozygous adenine/adenine (AA) genotype at IL13 rs20541 SNP (14.8% vs 3.7%) and a lower frequency of the guanosine/guanosine (GG) genotype (51.9% vs 55.6%), while AC patients had higher GG genotype (70.4% vs 55.6%) with no AA genotype detected, yet no significant difference was noticed (p = 7.053). A significantly higher serum periostin in asthmatic patients compared to controls was found (p = 0.005). Higher levels of serum periostin, although nonsignificant, were recorded in AC patients compared to controls (22.88 ± 10.01ng/mL and 17.51 ± 3.17ng/mL, respectively). Periostin was significantly higher in patients with IL13 AA and GA genotypes compared to those with GG genotype (p = 0.016). A significant positive correlation between serum periostin and serum IL13 among allergic patients was recorded (r = 0.352, p < 0.001). Conclusion: Among Egyptian patients, serum level of periostin is significantly associated with asthma and positively correlates with IL13 level supporting its utility as a diagnostic biomarker. IL13 rs20541 gene polymorphism does not seem to play an obvious role in asthma and AC, which requires further evaluation.