As a folk medicinal plant, Juglans mandshurica has been used for the treatment of cancer in China and Korea. Traditionally, J. mandshurica is decocted together with chicken eggs. Both the decoction and medicated eggs possess anti-tumor properties. Clarifying the constituents of the decoction and absorbed by the medicated eggs is essential for the investigation of the active principles of J. mandshurica. Herein, the medicated eggs were prepared by decocting raw chicken eggs, having unbroken shells, with the decoction of J. mandshurica. A systematic investigation of the chemical profile of the J. mandshurica decoction and the medicated egg extraction was conducted by HPLC-Q-TOF-MS2. In total, 93 peaks, including 45 tannins, 14 naphthalene derivatives, 17 organic acids, 3 diarylheptanoids, 4 lignans, 3 anthraquinones, 1 flavonoid glycoside, 3 amino acids, and 3 nitrogenous compounds, were tentatively identified in the decoction. In the medicated egg extraction, 44 peaks including 11 organic acids, 3 amino acids, 3 nitrogenous compounds, 8 naphthalene derivatives, 3 diarylheptanoids, 15 tannins, and 1 lignan were tentatively identified. The chemical profile presented provided a detailed overview of the polar chemical constituents in J. mandshurica and useful information for the research of bioactive compounds of this plant.