Challenge Mode

Challenge Modes are in-game options to change the difficulty of the game. There are currently 8 challenges, and once activated they cannot be deactivated on that save file. There are no rewards for completing the challenges, other than for bragging rights. The game is always designed to be 100% completable, even with all eight challenges active (although the methods may be different). The recommended challenges are selected by default, however, you can click on them to disable that challenge.

Challenge Mode Berries
If the No Oak Items challenge is active, the Chople, Kebia, Shuca and Charti Berries are unable to be obtained as they normally would be from the Farm as all four berries require Oak Items to be equipped in order to mutate. Instead, they become available for purchase from the Johto Berry Master.

All 6 Challenges Shiny Route Quest (A6CSRQ)
Many community members have developed and participate in a challenge that goes beyond what is offered via the standard Challenge Modes. A6CSRQ is defined as not only playing using all 6 challenges (A6C is also a popular challenge), but also capturing every Shiny Pokémon possible on each Route/Dungeon/Town etc. before proceeding to the next location in the game. More information can be found on the Pokéclicker Discord, the A6CSRQ Discord where there is an active leaderboard that is maintained, and the A6CSRQ Google Doc where there are more resources and an FAQ.