Proper knowledge and confidence regarding Endo-Perio relationship plays an important role in correct clinical decisions and management of these conditions. The aim of this study is to assess dentists' knowledge and understanding, in addition, their confidence regarding Endo-Perio relationship, consequently, to investigate the prevalence of misconceptions. This cross-sectional study, conducted from December 2021 to March 2022, utilized voluntary anonymous questionnaire, distributed among general dentists, graduates of King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia, year of 2021 (n = 151). The questionnaire had two parts, demographic and 13 closed ended scientific questions to assess knowledge and understanding with 4 points Likert scale after each question to assess confidence and misconceptions. Descriptive statistics and Chi-square test at a statistical significance of P-value <0.05 were conducted to analyze the data using SPSS. Total of 98 participants completed the questionnaire setting a response rate of (64.9%). Only (21.4%) had sufficient overall knowledge and understanding regarding Endo-Perio relationship with no significant association found between knowledge and gender (p = 0.8). A little more than one-third of our participants (37.83%) were overly confident; false confident, thus, had misconceptions. Our study revealed that the majority of our participants had deficient knowledge regarding Endo-Perio relationship. Thus, to compensate for this reported deficiency, changing teaching strategies and implementing continuing education courses are suggested. More studies assessing the interaction between knowledge and confidence in different dental topics are needed.