As the carriers of human wisdom and civilization, paper cultural relics such as manuscripts, documents and artistic works are non-renewable cultural resources and extremely valuable treasures of mankind. Unfortunately, a large number of long-stored paper cultural relics have been undergoing serious deterioration and discoloration due to the endogenous (pH, lignin, degradation products) and exogenous (light, heat, humidity, pollutant gases) factors. It is worth noting that the iron and copper metal species contained in some pigments and inks can cause serious corrosion and degradation of the paper. For example, the use of iron gall ink often produces perforation in inked areas due to the severe corrosion of paper. Moreover, the use of malachite (basic cupric carbonate) in traditional Chinese painting causes the yellowing or even embrittlement of nearby paper substrates; a remarkable yellowish-brown deteriorating edge can usually be observed near the green-blue pigment, which directly affects the readability and appreciation value of the art or even its stability in long-term preservation. The reasons for the damage of paper cultural relics containing iron/copper pigments are complex and diverse, and the reaction pathway and mechanism of degradation of cellulose polymers with iron/copper pigments are worthy of in-depth investigation. This article introduces the iron-based and copper-based pigments which are commonly used in paper cultural relics, including iron gall ink, Prussian blue, ocher, azurite, malachite, copper acetate, etc. We summarize three common routes of paper cellulose degradation, including acid hydrolysis, alkaline degradation and oxidative degradation. Then, we discuss the mechanism of acid-base reaction and redox reaction of paper cellulose under the participation of transition metal species. Among them, paper containing iron pigments mainly undergo Fenton oxidative degradation and acid hydrolysis. Correspondingly, the main pathways of paper corrosion by copper-containing pigments are Fehling oxidative degradation and alkaline degradation. This article focuses on the chemical reaction mechanisms of iron-based and copper-based pigments on the corrosion degradation of paper cultural relics, and concludes that the oxidation reaction involving iron and copper ions plays the main character in the accelerated degradation of paper cellulose. For this reason, adding antioxidants—including preventive antioxidants and chain-scission antioxidants—is proposed as a protection strategy to slow down the oxidation reaction of paper-based cultural relics. We focus on the use of complexing agents, such as phytic acid/phytate, ammonium bromide, protein gelatin and others, to coordinate the active iron/copper metal ions and slow down the oxidative degradation reaction. At the same time, some problems in the complexing method are revealed, e.g., phytic acid should be used under acidic condition, pigment discoloration will be caused by using benzotriazole, and some antioxidants may be toxic. Finally, this article proposes a prospect for the space to be explored in mechanism research and protection strategies of paper containing iron-based and copper-based pigments. With regard to mechanism research, the distribution of the free state and the complex state of the transition metal, the conditions for transition metal to initiate the oxidation reaction, and the relationship between the oxidation degradation reaction and the supramolecular structure of cellulose remain to be studied. With regard to protection strategies, the selected protection agents should not only effectively slow down the degradation rate of paper cellulose, but also not cause damage to paper fibers and pigments. This article proposes a more profound understanding of the mechanism of cellulose degradation and evolution caused by transition metal pigments from a chemical point of view and provides guidance and reference for the multi-directional protection of paper cultural relics containing transition metal pigments.