Black-bone fowls are rich in melanin and regarded as being rich in nutritional value. However, the metabolism of antibiotics in black-bone fowls remains poorly understood. This study aimed to determine the tissue residue depletion kinetics of Sulfamonomethoxine (SMM) or Doxycycline in Taihe black-bone silky fowls. The tissue residue experiments involved a total of two hundred and forty Taihe black-boned silky fowls. The birds were raised to 100 days old in the same laboratory conditions and divided into a control group, SMM group, and Doxycycline group (80 birds for each group). The control group was provided normal drinking water. The SMM group was oral-administered SMM at concentrations of 50 mg/kg bw per day, and the Doxycycline group was oral-administered Doxycycline at concentrations of 40 mg/kg bw for 5 days, respectively. After the last dose, liver, kidney, muscle, and skin/fat were collected at various time points (0.16, 1, 3, 5, 7, 9, 12, 20, 30, and 40 days, eight birds for each time point). Concentrations of SMM or Doxycycline were analyzed using the UPLC-MS/MS method. The terminal elimination half-lives of SMM in muscle, skin/fat, liver, and kidney were 1.82 ± 1.24, 15.3 ± 4.97, 4.36 ± 1.49, and 5.42 ± 3.46 days, respectively, and 8.62 ± 2.82, 6.88 ± 2.06, 4.12 ± 1.28, and 1.53 ± 0.28 days for Doxycycline. The estimated withdrawal times (WDIs) of SMM were 4, 27, 10, and 12 days, while the estimated WDIs of Doxycycline were 18, 15, 4, and 6 days for muscle, skin/fat, liver, and kidney, respectively. The SMM or Doxycycline bioaccumulate in the skin/fat and may cause antimicrobial residues to be absorbed by human when the skin/fat is used in the diet. Doxycycline persists in muscle for a longer duration compared to SMM. This highlights the significance of muscle and skin/fat as a target organ for future food safety research.