Background: The bupivacaine (BVC)/meloxicam (MLX) combination is the first extended-release dual-acting local anesthetic (DALA) that provides 72 h of postoperative pain relief. It reduces opioid use after surgery and manages pain better than BVC alone over 72 h, and overcomes surgical site inflammation with a new synergistic mode of action that combines BVC with a low dosage of MLX. Objective: In today’s pharmaceutical research, we take great care to only use non-toxic solvents that pose no threat to either humans or the environment. This work determines BVC and MLX simultaneously, utilizing water and 0.1 M HCl in water as solvents. Moreover, the eco-friendliness of the specified solvents and the whole method development steps was evaluated based on how user-friendly they were using four standard methodologies. Methods: The developed spectrophotometric methods depended on either zero-order, derivative, or ratio spectra that only required simple mathematical handling. The current techniques include dual wavelength (DW), Fourier self-deconvolution (FSD), first derivative (D1 ), ratio difference (RD), and first ratio derivative (DD1 ). Results: Linearity was confirmed over a concentration range of 50–700 lg/mL for BVC and 1–10 lg/mL for MLX. For BVC and MLX, the LOQs were 26.85–41.33 lg/mL and 0.21–0.95 lg/mL, while the LODs were 8.86–13.64 lg/mL and 0.06–0.31 lg/mL, respectively. For the full validation of the proposed methods, ICH (international conference on harmonization) criteria were followed. Conclusion: Current methods have the advantage of sticking to the basis of zero-order, derivative, or ratio spectra and needing just the barest minimum of data processing: no complex software, lengthy stages, or transformations are needed.