Background: Quality of life (QOL) for patients with Peptic ulcer disease (PUD) is of interest worldwide and disease-specific instruments are needed for clinical research and practice. This paper focus on the development and validation of the PUD scale under the system of Quality of Life Instruments for Chronic Diseases (QLICD-PU) by the modular approach and both classical test theory and Generalizability Theory. Methods: QLICD-PU is developed based on programmatic decision-making procedures, including multiple nominal and focus group discussions, in-depth interviews, and quantitative statistical procedures. Based on the data of 153 PUD inpatients, G and D studies using correlation analysis, factor analysis, t-test, and generalized theoretical analysis were used to assess the validity, reliability, and responsiveness of the scale.Results: When SF-36 was used as the standard, correlation and factor analysis confirmed good structural validity and standard-related validity of QLICD-PU. Except for the social domain (0.62), the internal consistency α of all domains is higher than 0.70. The overall score and the retest reliability coefficients (Pearson r and intra-class correlation ICC) in all domains are higher than 0.80 (0.77 in the social domain). After treatment, the overall scores and scores of all domains have statistically significant changes (P <0.01), except for social impact and sexual function scores. The SRM of field-level scores ranges from 0.34 to 1.03. The G coefficient and reliability index (Ф coefficient) further confirm the reliability of the scale through more accurate variance components and decision-making information about changes in the number of items.Conclusions: QLICD-PU can be used as a useful measurement to assess the quality of life of PUD patients with good psychometric characteristics and multiple advantages.