I recall you configuring a static IPv6 address for your Pi-hole machine before.
Would that still be the case?
Were you able to substantiate that e.g. by running nslookups against Pi-hole's IP addresses when that happened?
I rather suspect it to be another IPv6 configuration issue.
I don't think it's introduced by neither Pi-hole nor Wireguard.
But Wireguard may have triggered it if you had enabled IPv6 forwarding (net.ipv6.conf.<interface>.forwarding) for it, since IPv6 forwarding stops your OS acquring IPv6 RAs.
If that's the case, you may have to reenable IPv6 auto-configuration and RA acquisition by setting the respective entries for net.ipv6.conf.<interface>.autoconf and net.ipv6.conf.<interface>.accept_ra.
However, if you are still using a static IPv6, your network interface should at least still carry that static address, and the above wouldn't apply then.