Antibiotics are among the most widely used pharmaceutically active compounds. Possessing the capability to adversely impact the ecological system, existence of antibiotics in the environment is an escalating concern. With the purpose of removing two widely used antibiotics efficiently from aqueous solutions, the competency of two biochar (BC)-based sorbents derived from spent coffee (SC) grounds was investigated. Both pristine (SCBC) and nickel (II) oxide-impregnated (Ni-SCBC) biochars were utilized as sustainable and cost-effective sorbents to remove daunorubicin (DAYN) and tigecycline (TIGY) from single synthetic aqueous solutions and binary combinations. Batch adsorption experiments were controlled implementing Box–Behnken design. The removal efficiency of Ni-SCBC was superior compared to SCBC (TIGY: 67.06%, DAYN: 94.30%). Results of characterizations showed that impregnation with NiO changed the degree of crystallization with a remarkable increase in the surface area from 49.23 m2/g in SCBC to 86.06 m2/g in Ni-SCBC. Adsorption of DAYN and TIGY (single solutions) conformed well to Freundlich, and Langmuir isotherms, respectively. A maximum adsorption capacity (qmax) of 136.62 mg/g (DAYN) and 73.15 mg/g (TIGY) was reported in single solutions, compared to 23.50 mg/g (DAYN) and 58.42 mg/g (TIGY) in binary mixture. Adsorption kinetics onto Ni-SCBC fitted well with the pseudo-second-order (PSO) and Elovich models. Acquired results demonstrated that SCBC and Ni-SCBC are promising adsorbents for remedying antibiotics.